bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic structure in two highly diverse lineages of Tillandsia (Bromeliaceae)
Authors: Granados Mendoza Carolina , Granados-Aguilar Xochitl , Donadío Sabina , Salazar Gerardo A. , Flores-Cruz María , Hágsater Eric , Starr Julian R. , Ibarra-Manríquez Guillermo , Fragoso-Martínez Itzi , Magallón Susana
Published: March 2017

The Neotropical genus Tillandsia (Bromeliaceae) is an excellent model system for macroevolutionary and biogeographic studies owing to its remarkable species diversity (ca. 650 spp.) and varied morphological and ecological adaptations to epiphytic and saxicolous habitats. Recent phylogenetic studies have greatly improved our knowledge about generic limits and infrageneric classification of Tillandsia. These studies have identified two clades of Tillandsia characterized by a distinct geographic distribution: (i) a North and Central American clade that includes species from subgenus Tillandsia; and (ii) a central South American clade containing species from subgenera Aerobia, Anoplophytum, Diaphoranthema, and Phytarrhiza. Our study aimed to determine the size, composition, and potential geographic structure of these two clades within the context of a global phylogeny of Tillandsioideae. With the addition of 100 newly sequenced species to previous studies to cover the now ca. 30% of the known species diversity of Tillandsia, our analyses found both clades to be strongly supported, and revealed that their species richness is much greater than previously known. Ancestral area estimation suggests that most of the diversification of the first of these clades took place in North and Central America, whereas within the second, most of the migratory events occurred from the Andes to the Brazilian shield.
Seesaw model and two zero flavor neutrino texture
Authors: Kitabayashi Teruyuki , Yasuè Masaki
Published: March 2017

In the two zero flavor neutrino mass matrix scheme with nonvanishing Majorana effective mass [Formula: see text] for the neutrinoless double beta decay, four textures are compatible with observed data. We obtain the complete list of the possible textures of four zero Dirac neutrino mass matrix [Formula: see text] in the seesaw mechanism providing these four flavor neutrino textures. Explicit analytical analysis of [Formula: see text] turns out to provide the relation of [Formula: see text].
Phase noise analysis of voltage controlled oscillator used in cesium atomic clock
Authors: Zhi Menghui , Tang Liang , Qiao Donghai
Published: March 2017

Coherent population trapping (CPT) cesium frequency standard plays a significant role in precision guidance of missile and global positioning system (GPS). Low noise 4.596 GHz voltage controlled oscillator (VCO) is an indispensable part of microwave signal source in cesium frequency standard. Low-phase noise is also the most important and difficult performance indicator of VCO. Starting from phase noise analysis method proposed by Leeson, the formulas about the relationship between phase noise of output signal of oscillator feedback model and phase fluctuation spectrum of amplifier, phase noise of oscillator are derived in this paper. Finally, the asymptote model of microwave oscillator is proposed based on the formula derivation. The experiment shows that when the reverse bias voltage of variode is 1.8 V, the designed oscillation frequency of VCO is 4.596 GHz, the power is −1 dBm and the DC power consumption is 19.6 mW. The tendency of phase noise simulation curve and actual test curve conform to asymptote model. The phase noise in 1 and 10 kHz is, respectively, −60.86 and −86.58 dBc/Hz. The significance of the paper lies in determining the main factors influencing oscillator phase noise and providing guiding direction for the design of low-phase noise VCO.
Scavenging energy from the motion of human lower limbs via a piezoelectric energy harvester
Authors: Fan Kangqi , Yu Bo , Zhu Yingmin , Liu Zhaohui , Wang Liansong
Published: March 2017

Scavenging energy from human motion through piezoelectric transduction has been considered as a feasible alternative to batteries for powering portable devices and realizing self-sustained devices. To date, most piezoelectric energy harvesters (PEHs) developed can only collect energy from the uni-directional mechanical vibration. This deficiency severely limits their applicability to human motion energy harvesting because the human motion involves diverse mechanical motions. In this paper, a novel PEH is proposed to harvest energy from the motion of human lower limbs. This PEH is composed of two piezoelectric cantilever beams, a sleeve and a ferromagnetic ball. The two beams are designed to sense the vibration along the tibial axis and conduct piezoelectric conversion. The ball senses the leg swing and actuates the two beams to vibrate via magnetic coupling. Theoretical and experimental studies indicate that the proposed PEH can scavenge energy from both the vibration and the swing. During each stride, the PEH can produce multiple peaks in voltage output, which is attributed to the superposition of different excitations. Moreover, the root-mean-square (RMS) voltage output of the PEH increases when the walking speed ranges from 2 to 8 km/h. In addition, the ultra-low frequencies of human motion are also up-converted by the proposed design.
Routing optimization in networks based on traffic gravitational field model
Authors: Liu Longgeng , Luo Guangchun
Published: March 2017

For research on the gravitational field routing mechanism on complex networks, we further analyze the gravitational effect of paths. In this study, we introduce the concept of path confidence degree to evaluate the unblocked reliability of paths that it takes the traffic state of all nodes on the path into account from the overall. On the basis of this, we propose an improved gravitational field routing protocol considering all the nodes’ gravities on the path and the path confidence degree. In order to evaluate the transmission performance of the routing strategy, an order parameter is introduced to measure the network throughput by the critical value of phase transition from a free-flow phase to a jammed phase, and the betweenness centrality is used to evaluate the transmission performance and traffic congestion of the network. Simulation results show that compared with the shortest-path routing strategy and the previous gravitational field routing strategy, the proposed algorithm improves the network throughput considerably and effectively balances the traffic load within the network, and all nodes in the network are utilized high efficiently. As long as [Formula: see text], the transmission performance can reach the maximum and remains unchanged for different [Formula: see text] and [Formula: see text], which ensures that the proposed routing protocol is high efficient and stable.
Exploiting NoSQL Graph Databases and in Memory Architectures for Extracting Graph Structural Data Summaries
Authors: Castelltort Arnaud , Laurent Anne
Published: March 2017

NoSQL graph databases have been introduced in recent years for dealing with large collections of graph-based data. Scientific data and social networks are among the best examples of the dramatic increase of the use of such structures. NoSQL repositories allow the management of large amounts of data in order to store and query them. Such data are not structured with a predefined schema as relational databases could be. They are rather composed by nodes and relationships of a certain type. For instance, a node can represent a Person and a relationship Friendship. Retrieving the structure of the graph database is thus of great help to users, for example when they must know how to query the data or to identify relevant data sources for recommender systems. For this reason, this paper introduces methods to retrieve structural summaries. Such structural summaries are extracted at different levels of information from the NoSQL graph database. The expression of the mining queries is facilitated by the use of two frame-works: Fuzzy4S allowing to define fuzzy operators and operations with Scala; Cypherf allowing the use of fuzzy operators and operations in the declarative queries over NoSQL graph databases. We show that extracting such summaries can be impossible with the NoSQL query engines because of the data volume and the complexity of the task of automatic knowledge extraction. A novel method based on in memory architectures is thus introduced. This paper provides the definitions of the summaries with the methods to automatically extract them from NoSQL graph databases only and with the help of in-memory architectures. The benefit of our proposition is demonstrated by experimental results.
Mining Frequent Weighted Itemsets without Storing Transaction IDs and Generating Candidates
Authors: Lee Gangin , Yun Unil , Ryu Keun Ho
Published: March 2017

Weighted itemset mining, which is one of the important areas in frequent itemset mining, is an approach for mining meaningful itemsets considering different importance or weights for each item in databases. Because of the merit of the weighted itemset mining, various related works have been studied actively. As one of the methods in the weighted itemset mining, FWI (Frequent Weighted Itemset) mining calculates weights of transactions from weights of items and then finds FWIs based on the transaction weights. However, previous FWI mining methods still have limitations in terms of runtime and memory usage performance. For this reason, in this paper, we propose two algorithms for mining FWIs more efficiently from databases with weights of items. In contrast to the previous approaches storing transaction IDs for mining FWIs, the proposed methods employ new types of prefix tree structures and mine these patterns more efficiently without storing any transaction ID. Through extensive experimental results in this paper, we show that the proposed algorithms outperform state-of-the-art FWI mining algorithms in terms of runtime, memory usage, and scalability.
EFFECT OF MULLIGAN’S POSTEROLATERAL GLIDE ON SHOULDER ROTATOR STRENGTH, SCAPULAR UPWARD ROTATION IN SHOULDER PAIN SUBJECTS – A RANDOMIZED CONTROLLED TRIAL
Authors: Neelapala Y. V. Raghava , Reddy Y Ravi Shankar , Danait Roopa
Published: March 2017

Background and objectives: Joints may have an effect on the function of the surrounding muscles through nociceptors and mechanoreceptors. Pain reduction in the shoulder might lead to improved function of the muscles surrounding the shoulder in individuals with shoulder pain. The aim of our work was to determine the acute effect of Mulligan’s posterolateral glide on shoulder rotator strength, scapular motor control, and pain in painful shoulders. Methodology: Individuals with shoulder pain were randomly assigned to a control active exercise group and an experimental Mulligan’s posterolateral glide group. VAS, scapular upward rotation and shoulder rotator strength were the outcomes measured before and after three sessions of intervention. Multivariate analysis of variance (MANOVA) was used to analyze the differences between the groups after the intervention. Results: A total of 31 subjects with shoulder pain participated in the study. After the intervention, VAS scores ([Formula: see text] (1, 29) [Formula: see text] 27, [Formula: see text]) and Shoulder external rotator strength ([Formula: see text] (1, 29) [Formula: see text] 4.6, [Formula: see text]) were statistically significantly different between both the groups as revealed by one-way MANOVA. There were no significant differences found between the groups in scapular upward rotation ([Formula: see text] (1, 29) [Formula: see text] 0.09, [Formula: see text]) and internal rotator strength ([Formula: see text] (1, 29) [Formula: see text] 0.03, [Formula: see text]) post treatment. Pain scores were lesser and the external rotation strength was higher after Mulligans’ mobilization when compared to active exercise. Conclusion: Mulligan’s mobilization with posterolateral glide was effective in reducing pain and improving external rotator strength in individuals with painful shoulders when compare to active exercise. There were no significant differences noted in shoulder internal rotator strength and scapular upward rotation.
The earliest geological observations in Lithuania: a historical viewpoint
Authors: Grigelis A.
Published: March 2017

Our earliest knowledge of Lithuania's geology derives from historical data on the use of natural mineral resources in the daily life of its population, such as building stones, clay, chalk, amber and salt-bearing mineral waters. The first scientific data on geognosy appeared at the beginning of the eighteenth century in the works of educated monks. From the middle of the eighteenth century natural philosophy was taught at the Vilnius Academy. The last quarter of the eighteenth century is notable for the completion of the first geological maps compiled from field observations. The Department of Mineralogy was established in the secularized Vilnius University in 1803. Studies of mineralogy flourished there until the university's closure in 1832. Geological surveying was carried out under the auspices of the Russian Mines Department, which paid particular attention to the exploration of sources of salt, iron ores and coal. A number of localities of likely useful minerals were investigated, but they were not of sufficient quality to be economically viable. By the mid-nineteenth century, the geological survey in Lithuania had resulted in the recognition of Devonian, Jurassic, Cretaceous and Tertiary sedimentary rocks. Quaternary sediments were reported in hilly areas and sandy soils and notable occurrences of boulders were recorded in low-lying areas.
A BDI Game Master Agent for Computer Role-Playing Games
Authors: Luong Bao , Thangarajah John , Zambetta Fabio
Published: March 2017

In this paper we describe an approach for developing an intelligent game master (GM) for computer role-playing games. The role of the GM is to set up the game environment, manage the narrative ow and enforce the game rules whilst keeping the players engaged. Our approach is to use the popular Belief-Desire-Intention (BDI) model of agents to developing a GM. We describe the process for creating such a GM and how we implemented a prototype of it for a scenario in the Neverwinter Nights (NWN) game. We describe the evaluation of our prototype with human participants who played the chosen NWN scenario both with and without the BDI GM. The comparison survey completed by the participants shows that the system with the BDI GM was the clear winner with respect to game replayability, flexibility, objective setting and overall interest; thus, validating our hypothesis that a BDI GM will provide game players with a better gaming experience.
Strategies for Producing and Incorporating Conjugated Linoleic Acid–Rich Oils in Foods
Authors: Shinn Sara E. , Ruan Chuan Min , Proctor Andrew
Published: March 2017

Conjugated linoleic acid (CLA) is in ruminant-derived foods and is known to combat obesity-related diseases. However, CLA levels in a healthy diet are too low to produce a clinical effect. Therefore, CLA has been produced by linoleic isomerization through fermentation and chemical catalysis. Many of these techniques are not practical for food production, but a recent development has enabled production of CLA-rich triglyceride vegetable oils from high linoleic acid oils by a minor modification of conventional food-oil processing techniques. These oils were used to produce common lipid-based food, such as margarine, shortenings, and salad dressings, whose quality was enhanced by the presence of CLA-rich oil and provided a significant CLA source. Meat and egg CLA content and subsequent food quality can also be increased by addition of dietary CLA. However, consumer awareness of CLA benefits needs to increase prior to commercial-scale production of CLA-rich oil.
Rat Liver Enzyme Release Depends on Blood Flow‐Bearing Physical Forces Acting in Endothelium Glycocalyx rather than on Liver Damage
Authors: Díaz-Juárez Julieta A. , Hernández-Muñoz Rolando
Published: March 2017

We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH), apparently controlled by hemodynamic flow‐bearing physical forces. Here, we assess the involvement of stretch‐sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver “pool.” Moreover, liver enzyme release depended on extracellular calcium entry possibly mediated by stretch‐sensitive calcium channels, and this endothelial‐mediated mechanotransduction in liver enzyme release was also evidenced by modifying the glycocalyx carbohydrate components, directionality of perfusing flow rate, and the participation of nitric oxide (NO) and malondialdehyde (MDA), leading to modifications in the intracellular distribution of these enzymes mainly as nuclear enrichment of “mitochondrial” enzymes. In conclusion, the flow‐induced shear stress may provide fine‐tuned control of released hepatic enzymes through mediation by the endothelium glycocalyx, which provides evidence of a biological role of the enzyme release rather to be merely a biomarker for evaluating hepatotoxicity and liver damage, actually positively influencing progression of liver regeneration in mammals.
QELBY®-Induced Enhancement of Exclusion Zone Buildup and Seed Germination
Authors: Sharma Abha , Toso Dario , Kung Kurt , Bahng Gun-Woong , Pollack Gerald H.
Published: March 2017

A hydrophilic powder, QELBY, from the feldspar family of clay minerals was investigated for its ability to form structured or exclusion-zone (EZ) water. We demonstrated microsphere-free zones around different fractions of the QELBY powder or its hydrated pellet. Averaging approximately 100 μm, these zones grew to a size similar to that formed in the vicinity of the Nafion standard. In the case of silica (control), only occasional microsphere-free zones of about 70 μm were found. Further, studies to investigate QELBY’s energizing effect on germination and early sapling growth in brown chickpea seeds showed at least a 2-3-fold increase in root length and/or formation of shoots. This was seen in seeds bathed in QELBY supernatants or surrounded by QELBY powder outside the vials containing the seeds. This indirect effect was observed whether the QELBY was dry or hydrated.
Parent Training Occupational Therapy Program for Parents of Children with Autism in Korea
Authors: An Sun-Joung L.
Published: March 2017

Attitudes and beliefs about parent participation in occupational therapy are shifting toward family-centered practice worldwide. However, adopting a family-centered approach in a society such as Korea, where a Confucian culture of hierarchical roles is reflected in a strong medical model, can prove to be very difficult. A parent training program was developed at the HOPE Center, a pediatric occupational therapy center, to bridge the gap between the traditional medical model and the ideal family-centered model. This study examined the effectiveness of the parent training and gauged parents’ perceptions and experiences of a more family-centered approach to therapy. Four parent-child dyads living with autism participated in five months of parent training at the HOPE center. The results on the Canadian Occupational Performance Measure showed that the parent training improved the occupational performance of both children and parents. Six open-ended questions were used to investigate parents’ perceptions and experiences of parent training. Two broad themes emerged: improved self-efficacy and the cultural reality of living with autism in Korea. This study demonstrates that building parent training into an occupational therapy program may optimize the effectiveness of any therapy and introduce a more family-centered approach to therapy while maintaining cultural integrity.
A Case of Persistent Generalized Retrograde Autobiographical Amnesia Subsequent to the Great East Japan Earthquake in 2011
Authors: Odagaki Yuji
Published: March 2017

Functional retrograde autobiographical amnesia is often associated with physical and/or psychological trauma. On 11 March 2011, the largest earthquake on record in Japan took place, and subsequent huge tsunami devastated the Pacific coast of northern Japan. This case report describes a patient suffering from retrograde episodic-autobiographical amnesia for whole life, persisting for even more than five years after the disaster. A Japanese man, presumably in his 40s, got police protection in April 2016 but was unable to respond to question about his own name. He lost all information about his personal identity, and his memory was wholly lost until the disaster on 11 March 2011. He was able to recall his life after the disaster, and semantic memories and social abilities were largely preserved. A medical examination performed on 1 November 2016 verified that he was awake, alert, and oriented to time, place, and person (except for himself). General physical and neurological examinations revealed no pathological findings. He also experienced some symptoms associated with posttraumatic stress disorder (PTSD), such as intrusive thoughts, flashbacks, and nightmares. No abnormalities were detected by biochemical test and brain magnetic resonance imaging (MRI). Physicians and other professionals who take care of victims of disaster should be aware of dissociative spectrum disorders, such as psychogenic amnesia.
Regional Cerebral Blood Flow in Mild Cognitive Impairment and Alzheimer’s Disease Measured with Arterial Spin Labeling Magnetic Resonance Imaging
Authors: Sierra-Marcos Alba
Published: March 2017

Alzheimer’s disease (AD) depicts dynamic changes in regional brain function from early stages of the disease. Arterial spin labeling- (ASL-) based MRI methods have been applied for detecting regional cerebral blood flow (rCBF) perfusion changes in patients with AD and mild cognitive impairment (MCI). Nevertheless, the results obtained from ASL studies in AD and MCI are still controversial, since rCBF maps may show both hypoperfusion or hyperperfusion areas in brain structures involved in different cognitive functions. The goal of this review is to provide the current state of the art regarding the role of ASL for detecting distinctive perfusion patterns in subjects with MCI and/or AD. The ability to obtain this information using a noninvasive and widely available modality such as ASL should greatly enhance the knowledge into the broad range of hemodynamically related changes taking place during the cognitive decline process in AD.
Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases
Authors: Ying Shibo , Jiang Zhaoqiang , He Xianglei , Yu Min , Chen Riping , Chen Junqiang , Ru Guoqing , Chen Yuan , Chen Wanyuan , Zhu Lijin , Li Tao , Zhang Yixiao , Guo Xinnian , Yin Xianhong , Zhang Xing , Lou Jianlin
Published: March 2017

High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.
In Vitro Studies on the Degradability, Bioactivity, and Cell Differentiation of PRP/AZ31B Mg Alloys Composite Scaffold
Authors: Zou Jian , Shi Zhongmin , Xu Hongwei , Li Xiaolin
Published: March 2017

In recent years, more and more methods have been developed to improve the bioactivity of the biodegradable materials in bone tissue regeneration. In present study, we used rat mesenchymal stem cells (rMSCs) to evaluate the outcomes of Mg alloys (AZ31B, Magnesium, and Aluminum) and Platelet-rich plasma (PRP)/Mg alloys on rMSCs biocompatibility and osteogenic differentiation. Water absorption experiments indicated that both bare AZ31B and PRP/AZ31B were capable of absorbing large amounts of water. But the water absorption ratio for PRP/AZ31B was significantly higher than that for bare AZ31B. The degradability experiments implied that both samples degraded at same speed. rMSCs on the surface of AZ31B distributed more and better than those on the AZ31B scaffold. In ALP activity experiment, the activity of rMSCs on the PRP/AZ31B was markedly higher than that on the AZ31B scaffolds on the 7th day and 14th day. qRT-PCR also showed that OPN and OCN were expressed in both samples. OPN and OCN expression in PRP/AZ31B sample were higher than those in bare AZ31B samples. In summary, the in vitro study implied that AZ31B combined with PRP could remarkably improve cell seeding, attachment, proliferation, and differentiation.
Prevalence of Bacteriuria and Antimicrobial Susceptibility Patterns among Diabetic and Nondiabetic Patients Attending at Debre Tabor Hospital, Northwest Ethiopia
Authors: Worku Seble , Derbie Awoke , Sinishaw Mulusew Alemneh , Adem Yesuf , Biadglegne Fantahun
Published: March 2017

Background. Urinary tract infection is a major health problem especially in developing countries. Information about bacterial pathogens isolated from urinary tract infection in diabetic patients and their antimicrobial susceptibility patterns is limited in Ethiopia. Therefore, this study aimed at isolating bacterial pathogens and their antimicrobial susceptibility patterns.Methods. A hospital based comparative cross-sectional study was conducted at Debre Tabor. Urine sample was inoculated onto cysteine lysine electrolyte deficient (CLED) medium. Bacterial pathogens were identified using standard bacteriological methods. The data were cleaned and entered into SPSS version 20.Pvalue less than 0.05 is considered statistically significant.Result. A total of 384 study participants were included in the study. Of them, 21 (10.9%) were from diabetics and 9 (4.7%) of them were from nondiabetics. Large proportion of gram positive bacteria at 18 (58.1%) were isolated compared to gram negatives at 13 (41.9%). Gram positive isolates were resistant to cotrimoxazole 10 (58.8%).Conclusion. The isolation rates of bacterial pathogens were higher in diabetic than nondiabetic patients. Bacteriuria was significantly associated with sex and type of diabetes. Multidrug resistance to two or more antibiotics was observed in 56.7% of bacterial isolates. Rational use of antimicrobial agent should be thought of to prevent the emergence of multidrug resistance.
Association between STK11 Gene Polymorphisms and Coronary Artery Disease in Type 2 Diabetes in Han Population in China
Authors: Ma Xiaowei , Bai Ge , Lu Difei , Huang Linjuan , Zhang Jianwei , Deng Ruifen , Ding Shan , Gu Nan , Guo Xiaohui
Published: March 2017

Background. Recent studies indicated that the Serine threonine kinase 11 (STK11), which is a key regulator of the AMP-activated protein kinase (AMPK), plays a crucial role in cardiovascular system. This study aimed to investigate whether genetic variations in the STK11 gene affect the risk of coronary artery disease (CAD) in Chinese type 2 diabetics. Methods. 5 haplotype-tagging single nucleotide polymorphisms (SNPs) were selected, and 288 CAD-positive cases and 159 CAD-negative controls with type 2 diabetes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results. The carriers of minor allele A at rs12977689 had a higher risk of CAD compared to the homozygotes of CC (OR = 1.572, 95% CI = 1.039–2.376, p=0.035), and the difference was still significant after adjustment for the other known CAD risk factors (OR′ = 1.184, 95%  CI′ = 1.036–1.353, p′=0.013). Conclusion. Genetic variability at STK11 locus is associated with CAD risk in type 2 diabetes in the Chinese population.
Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin
Authors: Axelgaard Esben , Østergaard Jakob Appel , Thiel Steffen , Hansen Troels Krarup
Published: March 2017

Mannan-binding lectin (MBL) has been reported to be involved in the pathophysiology of diabetic nephropathy. MBL is a pattern-recognition molecule of the innate immune system that initiates the lectin pathway of the complement system upon recognition of evolutionary conserved pathogen-associated molecular patterns or to altered self-tissue. Our group have previously shown direct effects of MBL on diabetes-induced kidney damage, and we hypothesized that MBL may cause autoactivation of the complement system via binding to neoepitopes induced by hyperglycemia. In the present study, we induced diabetes in MBL knockout mice and in wild type C57BL/6J mice by low-dose streptozotocin injection and measured blood glucose and urine albumin-to-creatinine ratio to monitor development of diabetes. After 24 weeks, fluorescently labelled recombinant MBL was injected intravenously in diabetic MBL knockout mice after which the distribution was investigated using in vivo fluorescence imaging. Mice were subjected to in vivo and ex vivo imaging 24 hours after injection. MBL was found to accumulate in the kidneys of diabetic mice as compared to healthy control mice (p<0.0001). These findings support the hypothesis of a significant role of MBL and the complement system in the pathophysiology of diabetic nephropathy.
Maxillofacial Prosthesis in Dentofacial Traumas: A Retrospective Clinical Study and Introduction of New Classification Method
Authors: Brauner Edoardo , Pompa Giorgio , Quarato Alessandro , Jamshir Sara , De Angelis Francesca , Di Carlo Stefano , Valentini Valentino
Published: March 2017

Background. Maxillofacial trauma represents a field of common interest as regards both the maxillofacial surgery and prosthodontics, especially for the functional and aesthetic stomatognathic rehabilitation. This condition necessitates relationship between maxillofacial surgeon and prosthodontist, to achieve the ultimate treatment goal.Purpose. The purpose of this study is to make predictable patients outcomes classifying their clinical data, using certain parameters and introducing a new classification method.Materials and Methods. We have chosen 7 parameters to classify the entity of the damage of these patients and to make their treatment and their prognosis predictable: number of teeth lost (T1–T4), upper/lower maxilla (U/L), alveolar/basal bone (Alv/B), gingival tissues (G), soft tissues (S), adult/child (a/c), and reconstructed patient (R).Results and Conclusions. The multidisciplinary approach and the collaboration between multiple clinical figures are therefore critical for the success of the treatment of these patients. The presence and quantification of above parameters influence the treatment protocol; patients undergo different levels of treatment depending on the measured data. The recognition of certain clinical parameters is fundamental to frame diagnosis and successful treatment planning.
Adenoid Cystic Carcinoma of the Uterine Cervix: A Report of 2 Cases
Authors: Rais Meryem , Kharmoum Jinane , Ech-Charif Soumaya , El Khannoussi Basma
Published: March 2017

Adenoid cystic carcinoma is malignant tumor that exceptionally occurs in the uterine cervix. It is mostly seen in postmenopausal women and has an aggressive clinical course. We report two cases of an adenoid cystic carcinoma associated with a high grade squamous intraepithelial lesion and invasive squamous cell carcinoma of the uterine cervix and discuss briefly its clinical and pathological characteristics.
HDAC Inhibitor Panobinostat Engages Host Innate Immune Defenses to Promote the Tumoricidal Effects of Trastuzumab in HER2+ Tumors
Authors: Medon Mikolaj , Vidacs Eva , Vervoort Stephin J , Li Jason , Jenkins Misty R. , Ramsbottom Kelly M. , Trapani Joseph A. , Smyth Mark J. , Darcy Phillip K. , Atadja Peter W. , Henderson Michael A. , Johnstone Ricky W. , Haynes Nicole M.
Published: March 2017

Histone deacetylase inhibitors (HDACi) may engage host immunity as one basis for their antitumor effects. Herein, we demonstrate an application of this concept using the HDACi panobinostat to augment the antitumor efficacy of trastuzumab (anti-HER2) therapy, through both tumor cell autonomous and nonautonomous mechanisms. In HER2+ tumors that are inherently sensitive to the cytostatic effects of trastuzumab, cotreatment with panobinostat abrogated AKT signaling and triggered tumor regression in mice that lacked innate and/or adaptive immune effector cells. However, the cooperative ability of panobinostat and trastuzumab to harness host anticancer immune defenses was essential for their curative activity in trastuzumab-refractory HER2+ tumors. In trastuzumab-resistant HER2+ AU565pv xenografts and BT474 tumors expressing constitutively active AKT, panobinostat enhanced the antibody-dependent cell-mediated cytotoxicity function of trastuzumab. IFNγ–mediated, CXCR3-dependent increases in tumor-associated NK cells underpinned the combined curative activity of panobinostat and trastuzumab in these tumors. These data highlight the immune-enhancing effects of panobinostat and provide compelling evidence that this HDACi can license trastuzumab to evoke NK-cell–mediated responses capable of eradicating trastuzumab-refractory HER2+ tumors. Cancer Res; 77(10); 2594–606. ©2017 AACR.
Acquired Resistance with Epigenetic Alterations Under Long-Term Antiangiogenic Therapy for Hepatocellular Carcinoma
Authors: Ohata Yoshiteru , Shimada Shu , Akiyama Yoshimitsu , Mogushi Kaoru , Nakao Keisuke , Matsumura Satoshi , Aihara Arihiro , Mitsunori Yusuke , Ban Daisuke , Ochiai Takanori , Kudo Atsushi , Arii Shigeki , Tanabe Minoru , Tanaka Shinji
Published: March 2017

Antiangiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma; however, they finally relapse and progress, resulting in poor prognosis. We here established in vivo drug-tolerant subclones of human hepatocellular carcinoma cells by long-term treatment with VEGF receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin β 4 (Tβ4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones. Highlighting epigenetic alterations involved in drug resistance, we revealed that Tβ4 could be aberrantly expressed following demethylation of DNA and active modification of histone H3 at the promoter region. Ectopic overexpression of Tβ4 in hepatocellular carcinoma cells could significantly enhance sphere-forming capacities and infiltrating phenotypes in vitro, and promote growth of tumors refractory to the VEGFR multikinase inhibitor sorafenib in vivo. Clinically, sorafenib failed to improve the progression-free survival in patients with Tβ4-high hepatocellular carcinoma, indicating that Tβ4 expression could be available as a surrogate marker of susceptibility to this drug. This study suggests that Tβ4 expression triggered by epigenetic alterations could contribute to the development of resistance to antiangiogenic therapy by the acquisition of stemness, and that epigenetic control might be one of the key targets to regulate the resistance in hepatocellular carcinoma. Mol Cancer Ther; 16(6); 1155–65. ©2017 AACR.
Abstract A31: Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis
Authors: Liu Chun , Bronson Roderick T. , Wang Xiang-Dong
Published: March 2017

Ulcerative colitis is a risk factor for colon cancer. Dietary lutein, a nutrient rich in kale, is inversely associated with the risk of developing colon cancer in human observational epidemiologic studies. Besides lutein, kale also contains abundant amounts of other bioactive components with anti-inflammatory, antioxidant, and anti-cancer properties. As a whole food approach, kale may provide more favorable biologic effects on colonic inflammation and neoplasia than lutein alone. Additionally, it is unclear if lutein prevents colon neoplasia via the inhibition of colonic inflammation. Using a dextran sulfate sodium (DSS)-induced colitis and neoplasia mouse model, we evaluated the effects of dietary lutein supplementation and kale on the DSS-induced colorectal inflammation, ulceration, hyperplasia, dysplasia and cancer. Two hundred sixty four 8-week old Swiss-Webster (CFW) mice were assigned to one of ten groups (n = 26 to 27 in each group [13 males and 13 to 14 females]) for 21 weeks as follows: 1) 0.0005% of lutein plus DSS; 2) 0.001% of lutein plus DSS; 3) 0.002% of lutein plus DSS; 4) 0.005% of lutein plus DSS; 5) kale equivalent to 0.0005% of lutein plus DSS; 6) kale equivalent to 0.001% of lutein plus DSS; 7) kale equivalent to 0.002% of lutein plus DSS; 8) kale equivalent to 0.005% of lutein plus DSS; 9) DSS only; and 10) control with no treatment. During the 21-week experimental period, mouse body weights were recorded weekly. At week 7, the mice in groups 1-9 were given DSS for 4 cycles (1 cycle = 1 week 3% of DSS in drinking water followed by 2-week water) to induce colitis and colorectal neoplasia. This report described the findings on the presence of clinical signs of colitis (hemoccult and loose stools, which were evaluated at the end of each week throughout the experiments), and the findings from histopathological evaluations (inflammation, ulceration, hyperplasia, dysplasia, and neoplasia). Dietary lutein and kale, particularly two higher doses (0.002% and 0.005%), reduced the DSS-induced hemoccult and loose stools, as well as the DSS-induced inflammation, ulceration, hyperplasia, dysplasia, and neoplasia. These data suggest that dietary lutein and kale may prevent the DSS-induced colorectal inflammation and associated preneoplastic and neoplastic lesions.

Grant Funding Sources: This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2014-67017-21754 from the USDA National Institute of Food and Agriculture and by USDA/ARS grant 1950-51000-074S.

Citation Format: Chun Liu, Roderick T. Bronson, Xiang-Dong Wang. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A31.
Abstract A59: Glycosylation dynamically tunes the biophysical properties of the cancer cell glycocalyx
Authors: Shurer Carolyn , Paszek Matthew
Published: March 2017

Muc1 is a large, heavily O-glycosylated membrane protein that is overexpressed in the majority of cancers and constitutes the major structural element of the cancer cell glycocalyx. While the biophysical properties of the glycocalyx directly regulate cell-ECM adhesion, cell-cell interactions, and receptor spatial organization, how these properties change dynamically during acquisition of a metastatic phenotype is largely unknown. To dissect the relationship among glycan biosynthesis, mucin rigidity, and the bulk properties of the cancer-specific glycocalyx, we isolated sub-populations of Muc1-expressing breast epithelial cells that present with distinct mucin glycophenotypes. Remarkably, alterations in glycosylation were associated with profound differences in glycocalyx structure, even in isogenic cell lines. In one stable glycophenotype, cellular mucins were highly rigid and mechanically disrupted integrin adhesion, resulting in complete dissociation of cells from the substrate. On the other extreme, we isolated a stable population of cells that expresses high levels of Muc1, but these mucins were apparently flexible and had no observable effect on cell adhesion or motility. Based on lectin profiling, we identified specific patterns of Muc1 O-glycosylation associated with the two extremes in glycocalyx structures. Of notable significance, we discovered that metabolic reprogramming by the H-Ras oncogene could induce a glycophenotype consistent with mechanically rigid mucins. Future studies will identify the specific glycosylation machinery associated with the different glycophenotypes, with the hope of identifying new avenues of therapeutic intervention based on normalizing the mechano-phenotype of the cancer cell glycocalyx.

Citation Format: Carolyn Shurer, Matthew Paszek. Glycosylation dynamically tunes the biophysical properties of the cancer cell glycocalyx. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A59.
Abstract P1-05-18: Genomic copy number alterations (CNA) associated with pCR in HER2-positive (HER2+) early-stage breast cancer (BrCa) patients receiving neoadjuvant trastuzumab (T)
Authors: Walsh N , Gullo G , Maguire A , O'Donovan N , Quinn C , Crown J
Published: March 2017

Introduction: Genetic alterations such as amplifications and deletions frequently contribute to tumorigenesis. These alterations can change gene expression which alters the normal cell growth and survival regulatory mechanisms. Characterisation of DNA copy number alterations (CNA) is important to understand cancer progression and response to therapy. The aim of this study is to determine patterns of CNAs in HER2+ early-stage BrCa patients achieving pathological complete response (pCR) to neoadjuvant T therapy.

Methods: Retrospective analysis of our database of 95 HER2+ BrCa (stages I-III) who received T neoadjuvantly revealed 46 % (44/95) achieved pCR compared with 53 % (51/95) who did not respond (NR). DNA from pre-treatment tumour biopsy specimens from neoadjuvant T therapy patients was extracted, and array-based comparative genomic hybridization (aCGH, n = 8; 6 pCR:2 NR) was used to identify CNAs, which correlated with pCR. Pathway analysis was then used to identify functionally relevant genes in aberrant regions.

Results: aCGH analysis of DNA from pCR and NR identified distinct patterns of CNAs. HER2 amplicon was confirmed by IHC and aCGH in all samples. Although there was no significant difference in the average CNAs between groups (20±17 vs 17±2), there was greater variation in the range of CNAs in pCR (8-56 CNA) compared to NR (15-19 CNA). More gains and amplifications were observed in pCR patients with more deletions in the NR group. The most common chromosomal amplification region included chr8q12.1-q24 with 87.5% of all cases displaying gains. Of the 6 patients who achieved pCR, 50% displayed a deletion in chr9 spanning p24.3-p21.3, consistent with a deletion of tumour suppressor CDKN2A. No aberrations in chr9 were observed in NR cohort. The deleted genomic region contained 65 common protein-coding genes, with the interferon biological pathway as the most significant (p=1.03E-36).

Conclusions: Distinct genomic CNAs were observed between patients achieving pCR compared to NR. However, of the 8 pts characterised here, none have relapsed. Follow-up data revealed a relapse rate of 6.8 % (3/44) vs 11.8 % (6/51) in the pCR and NR groups, respectively. To further elucidate the immunological response, we will present CNA data patterns on relapse and response and compare the impact of CNAs, immune-related proteins and pCR as surrogate predictors for outcome.

Citation Format: Walsh N, Gullo G, Maguire A, O'Donovan N, Quinn C, Crown J. Genomic copy number alterations (CNA) associated with pCR in HER2-positive (HER2+) early-stage breast cancer (BrCa) patients receiving neoadjuvant trastuzumab (T) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-18.
Abstract P3-05-07: Flutamide reduced tumor progression and altered steroid hormone secretion in human and canine inflammatory breast cancer cell lines
Authors: Caceres S , Pena L , Silvan G , Illera MJ , Monsalve B , Woodward WA , Reuben J , Illera JC
Published: March 2017

Background: Inflammatory breast carcinoma (IBC) is a special type of breast cancer with a poor survival rate and accounts for 6% of diagnosed breast cancers. The role of androgens on breast cancer is on rise in research, trying to propose anti-androgen therapeutic strategies. The aim of this study was to determine the effects in vivo and in vitro of flutamide (anti-androgen drug) on cell proliferation, tumor progression and steroid production in two cancer IBC triple negative cell lines (SUM-149 and IPC-366, human and canine, respectively). Material and Methods: IPC-366 was cultured in Dulbecco's modified Eagle medium nutrient mixture F-12 Ham (DMEM/F12) and SUM149 was maintained in Ham's F-12 media. Flutamide concentrations added to the culture media were: 5 µm, 10 µm, and 15 µm for 72 hours. Additionally, IPC-366 and SUM149 xenotrasplanted mice were used for in vivo assays with the same flutamide concentrations administrated subcutaneously. Steroid hormones determination in culture media and tumor homogenates (pregnenolone (P5), progesterone (P4), dihydroepiandrostenedione (DHEA), androstenedione (A4), testosterone (T), dihydritestosterone (DHT), 17β-estradiol (E2) and estrone sulphate (SO4E1)) were assayed by EIA previously validated. Immunohistochemical (IHC) analysis of the steroidogenic enzymes CYP11A1, 3β-HSD, CYP19A1, 17β-HSD and 5α-reductase were assayed. Results: Percentage of cell proliferation showed a decrease in all treatments in IPC-366 and SUM149. In vivo tumor progression was reduced in around 65% in IPC-366 and SUM149 xenotrasplanted mice. Regarding hormonal secretion assayed in pellets and homogenates. in treated groups there was an increased in steroid secretion as showed the high levels found in P5, P4 and A4. T and DHT concentrations were higher in treated groups, in contrast to E2 levels that decreased. 17β-HSD and 5α-reductase by IHC showed a high expression in treated groups. Conclusion: IPC-366 and SUM149 treated with flutamide reduced the proliferation of neoplastic cells, reduced tumor progression in xenotrasplanted mice and altered steroid hormone secretion by increasing T production and decreasing in E2 levels. These results open a future approach for IBC and triple negative breast cancer.

Citation Format: Caceres S, Pena L, Silvan G, Illera MJ, Monsalve B, Woodward WA, Reuben J, Illera JC. Flutamide reduced tumor progression and altered steroid hormone secretion in human and canine inflammatory breast cancer cell lines [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-05-07.