bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward demand-aware networking
Authors: Avin Chen , Schmid Stefan
Published: January 2019

The physical topology is emerging as the next frontier in an ongoing effort to render communication networks more flexible. While first empirical results indicate that these flexibilities can be exploited to reconfigure and optimize the network toward the workload it serves and, e.g., providing the same bandwidth at lower infrastructure cost, only little is known today about the fundamental algorithmic problems underlying the design of reconfigurable networks. This paper initiates the study of the theory of demand-aware, self-adjusting networks. Our main position is that self-adjusting networks should be seen through the lense of self-adjusting datastructures. Accordingly, we present a taxonomy classifying the different algorithmic models of demand-oblivious, fixed demand-aware, and reconfigurable demand-aware networks, introduce a formal model, and identify objectives and evaluation metrics. We also demonstrate, by examples, the inherent advantage of demand-aware networks over state-of-the-art demand-oblivious, fixed networks (such as expanders). We conclude by observing that the usefulness of self-adjusting networks depends on the spatial and temporal locality of the demand; as relevant data is scarce, we call for community action.
Refining network intents for self-driving networks
Authors: Jacobs Arthur Selle , Pfitscher Ricardo José , Ferreira Ronaldo Alves , Granville Lisandro Zambenedetti
Published: January 2019

Recent advances in artificial intelligence (AI) offer an opportunity for the adoption of self-driving networks. However, network operators or home-network users still do not have the right tools to exploit these new advancements in AI, since they have to rely on low-level languages to specify network policies. Intent-based networking (IBN) allows operators to specify high-level policies that dictate how the network should behave without worrying how they are translated into configuration commands in the network devices. However, the existing research proposals for IBN fail to exploit the knowledge and feedback from the network operator to validate or improve the translation of intents. In this paper, we introduce a novel intent-refinement process that uses machine learning and feedback from the operator to translate the operator's utterances into network configurations. Our refinement process uses a sequence-to-sequence learning model to extract intents from natural language and the feedback from the operator to improve learning. The key insight of our process is an intermediate representation that resembles natural language that is suitable to collect feedback from the operator but is structured enough to facilitate precise translations. Our prototype interacts with a network operator using natural language and translates the operator input to the intermediate representation before translating to SDN rules. Our experimental results show that our process achieves a correlation coefficient squared (
i.e.,
R-squared) of 0.99 for a dataset with 5000 entries and the operator feedback significantly improves the accuracy of our model.
Datasets column
Authors: Dellandréa Emmanuel , Huigsloot Martijn , Chen Liming , Baveye Yoann , Xiao Zhongzhe , Sjöberg Mats
Published: January 2019

Affective video content analysis aims at the automatic recognition of emotions elicited by videos. It has a large number of applications, including mood based personalized content recommendation, video indexing, and efficient movie visualization and browsing. Beyond the analysis of existing video material, affective computing techniques can also be used to generate new content, e.g., movie summarization, personalized soundtrack recommendation to make user-generated videos more attractive. Affective techniques can furthermore be used to enhance the user engagement with advertising content by optimizing the way ads are inserted inside videos.
Therapeutic Antisense Oligonucleotides Are Coming of Age
Authors: Bennett C. Frank
Published: January 2019

The first published description of therapeutic applications of antisense oligonucleotide (ASO) technology occurred in the late 1970s and was followed by the founding of commercial companies focused on developing antisense therapeutics in the late 1980s. Since the late 1980s, there has been steady progress in improving the technology platform, taking advantage of advances in oligonucleotide chemistry and formulations as well as increased understanding of the distribution and safety of ASOs. There are several approved ASO drugs and a broad pipeline in development. In addition, advances in understanding human disease, including the genetic basis for most monogenic diseases and the availability of the full human genome sequence, have created numerous therapeutic applications for the technology. I summarize the state of the technology and highlight how advances in the technology position ASOs to be an important contributor to future medicines.
Imaging of Prostate-Specific Membrane Antigen with Small-Molecule PET Radiotracers: From the Bench to Advanced Clinical Applications
Authors: Rowe Steven P. , Gorin Michael A. , Pomper Martin G.
Published: January 2019

In recent years, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) labeled with radionuclides that allow for positron emission tomography (PET) imaging have been extensively studied in many clinical contexts in men with prostate cancer (PCa). The high sensitivity and specificity of these agents for identifying sites of PCa has quickly led to their widespread adoption as a de facto clinical standard of care throughout much of the world. PSMA-targeted PET radiotracers have been particularly well-studied in preoperatively staging men with high-risk PCa, evaluating biochemical recurrence following definitive therapy, and guiding metastasis-directed therapy in patients suspected of having oligorecurrent/oligometastatic disease. Furthermore, the expression of PSMA on the tumor neovasculature of many nonprostate malignancies has enabled a burgeoning subfield concentrated on delineating the potential utility of PSMA-targeted PET agents for imaging other cancers. In this review, we highlight the preclinical development of key small molecules that are now being clinically utilized for PCa imaging, discuss the roles of PSMA-targeted agents in guiding patient management, and consider the role these compounds may play in imaging nonprostate cancers.
Ethics of Human Genome Editing
Authors: Coller Barry S.
Published: January 2019

Advances in human genome editing, in particular the development of the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 method, have led to increasing concerns about the ethics of editing the human genome. In response, the US National Academy of Sciences and the National Academy of Medicine constituted a multidisciplinary, international committee to review the current status and make recommendations. I was a member of that committee, and the core of this review reflects the committee's conclusions. The committee's report, issued in February 2017, recommends the application of current ethical and regulatory standards for gene therapy to somatic (nonheritable) human genome editing. It also recommends allowing experimental germline genome editing to proceed if ( a) it is restricted to preventing transmission of a serious disease or condition, ( b) the edit is a modification to a common DNA sequence known not to be associated with disease, and ( c) the research is conducted under a stringent set of ethical and regulatory requirements. Crossing the so-called red line of germline genome editing raises important bioethical issues, most importantly, serious concern about the potential negative impact on individuals with disabilities. This review highlights some of the major ethical considerations in human genome editing in light of the report's recommendations.
Structure-Based Vaccine Antigen Design
Authors: Graham Barney S. , Gilman Morgan S.A. , McLellan Jason S.
Published: January 2019

Enabled by new approaches for rapid identification and selection of human monoclonal antibodies, atomic-level structural information for viral surface proteins, and capacity for precision engineering of protein immunogens and self-assembling nanoparticles, a new era of antigen design and display options has evolved. While HIV-1 vaccine development has been a driving force behind these technologies and concepts, clinical proof-of-concept for structure-based vaccine design may first be achieved for respiratory syncytial virus (RSV), where conformation-dependent access to neutralization-sensitive epitopes on the fusion glycoprotein determines the capacity to induce potent neutralizing activity. Success with RSV has motivated structure-based stabilization of other class I viral fusion proteins for use as immunogens and demonstrated the importance of structural information for developing vaccines against other viral pathogens, particularly difficult targets that have resisted prior vaccine development efforts. Solving viral surface protein structures also supports rapid vaccine antigen design and application of platform manufacturing approaches for emerging pathogens.
Anesthetic MS-222 eliminates nerve and muscle activity in frogs used for physiology teaching laboratories
Authors: Medler Scott
Published: January 2019

Frogs are routinely used in physiology teaching laboratories to demonstrate important physiological processes. There have been recent directives that promote the use of the anesthetic MS-222 (tricaine methanesulfonate), rather than lowering body temperature with a cold water bath to prepare reptiles and amphibians for physiological experiments or euthanasia. Indeed, the most recent edition of the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals proclaims that chilling in water is not an appropriate method and advocates for the usage of MS-222 or other anesthetics. However, prominent researchers have responded to this position by highlighting evidence that cooling ectothermic vertebrates is, in fact, an effective and appropriate method. Furthermore, MS-222 is a known voltage-gated Na+ channel blocker, and this anesthetic’s impact on the physiology of excitable tissues suggests that its use might be incompatible with experiments on nerve and muscle tissues. In the present study, I examined the effects of MS-222 at a concentration of 1.5 g/l on nerve, skeletal muscle, and cardiac muscle physiology of frogs. I found that immersion of frogs in this anesthetic blocked basic nerve and muscle physiology, making the frogs unsuitable for laboratory experiments. Applying MS-222 directly to the sciatic nerve dramatically blocked normal excitation-contraction coupling in skeletal muscle preparations, and direct application to the heart caused the organs to stop contracting. Based on these results, I conclude that MS-222 at the concentration studied may be incompatible with physiological preparations that rely on electrically excitable tissues for their normal function. Physiology educators who must use MS-222 with frogs should empirically determine an appropriate dosage and recovery time before using the anesthetic in the teaching laboratory.
Glucose-mediated inhibition of calcium-activated potassium channels limits α-cell calcium influx and glucagon secretion
Authors: Dickerson Matthew T. , Dadi Prasanna K. , Altman Molly K. , Verlage Kenneth R. , Thorson Ariel S. , Jordan Kelli L. , Vierra Nicholas C. , Amarnath Gautami , Jacobson David A.
Published: January 2019

Pancreatic α-cells exhibit oscillations in cytosolic Ca2+(Ca2+c), which control pulsatile glucagon (GCG) secretion. However, the mechanisms that modulate α-cell Ca2+coscillations have not been elucidated. As β-cell Ca2+coscillations are regulated in part by Ca2+-activated K+(Kslow) currents, this work investigated the role of Kslowin α-cell Ca2+handling and GCG secretion. α-Cells displayed Kslowcurrents that were dependent on Ca2+influx through L- and P/Q-type voltage-dependent Ca2+channels (VDCCs) as well as Ca2+released from endoplasmic reticulum stores. α-Cell Kslowwas decreased by small-conductance Ca2+-activated K+(SK) channel inhibitors apamin and UCL 1684, large-conductance Ca2+-activated K+(BK) channel inhibitor iberiotoxin (IbTx), and intermediate-conductance Ca2+-activated K+(IK) channel inhibitor TRAM 34. Moreover, partial inhibition of α-cell Kslowwith apamin depolarized membrane potential ( Vm) (3.8 ± 0.7 mV) and reduced action potential (AP) amplitude (10.4 ± 1.9 mV). Although apamin transiently increased Ca2+influx into α-cells at low glucose (42.9 ± 10.6%), sustained SK (38.5 ± 10.4%) or BK channel inhibition (31.0 ± 11.7%) decreased α-cell Ca2+influx. Total α-cell Ca2+cwas similarly reduced (28.3 ± 11.1%) following prolonged treatment with high glucose, but it was not decreased further by SK or BK channel inhibition. Consistent with reduced α-cell Ca2+cfollowing prolonged Kslowinhibition, apamin decreased GCG secretion from mouse (20.4 ± 4.2%) and human (27.7 ± 13.1%) islets at low glucose. These data demonstrate that Kslowactivation provides a hyperpolarizing influence on α-cell Vmthat sustains Ca2+entry during hypoglycemic conditions, presumably by preventing voltage-dependent inactivation of P/Q-type VDCCs. Thus, when α-cell Ca2+cis elevated during secretagogue stimulation, Kslowactivation helps to preserve GCG secretion.
Lipid and glucose metabolism in hepatocyte cell lines and primary mouse hepatocytes: a comprehensive resource for in vitro studies of hepatic metabolism
Authors: Nagarajan Shilpa R. , Paul-Heng Moumita , Krycer James R. , Fazakerley Daniel J. , Sharland Alexandra F. , Hoy Andrew J.
Published: January 2019

The liver is a critical tissue for maintaining glucose, fatty acid, and cholesterol homeostasis. Primary hepatocytes represent the gold standard for studying the mechanisms controlling hepatic glucose, lipid, and cholesterol metabolism in vitro. However, access to primary hepatocytes can be limiting, and therefore, other immortalized hepatocyte models are commonly used. Here, we describe substrate metabolism of cultured AML12, IHH, and PH5CH8 cells, hepatocellular carcinoma-derived HepG2s, and primary mouse hepatocytes (PMH) to identify which of these cell lines most accurately phenocopy PMH basal and insulin-stimulated metabolism. Insulin-stimulated glucose metabolism in PH5CH8 cells, and to a lesser extent AML12 cells, responded most similarly to PMH. Notably, glucose incorporation in HepG2 cells were 14-fold greater than PMH. The differences in glucose metabolic activity were not explained by differential protein expression of key regulators of these pathways, for example glycogen synthase and glycogen content. In contrast, fatty acid metabolism in IHH cells was the closest to PMHs, yet insulin-responsive fatty acid metabolism in AML12 and HepG2 cells was most similar to PMH. Finally, incorporation of acetate into intracellular-free cholesterol was comparable for all cells to PMH; however, insulin-stimulated glucose conversion into lipids and the incorporation of acetate into intracellular cholesterol esters were strikingly different between PMHs and all tested cell lines. In general, AML12 cells most closely phenocopied PMH in vitro energy metabolism. However, the cell line most representative of PMHs differed depending on the mode of metabolism being investigated, and so careful consideration is needed in model selection.
Motion Planning of Autonomous Mobile Robot Using Recurrent Fuzzy Neural Network Trained by Extended Kalman Filter
Authors: Zhu Qidan , Han Yu , Liu Peng , Xiao Yao , Lu Peng , Cai Chengtao
Published: January 2019

This paper proposes a novel motion planning method for an autonomous ground mobile robot to address dynamic surroundings, nonlinear program, and robust optimization problems. A planner based on the recurrent fuzzy neural network (RFNN) is designed to program trajectory and motion of mobile robots to reach target. And, obstacle avoidance is achieved. In RFNN, inference capability of fuzzy logic and learning capability of neural network are combined to improve nonlinear programming performance. A recurrent frame with self-feedback loops in RFNN enhances stability and robustness of the structure. The extended Kalman filter (EKF) is designed to train weights of RFNN considering the kinematic constraint of autonomous mobile robots as well as target and obstacle constraints. EKF’s characteristics of fast convergence and little limit in training data make it suitable to train the weights in real time. Convergence of the training process is also analyzed in this paper. Optimization technique and update strategy are designed to improve the robust optimization of a system in dynamic surroundings. Simulation experiment and hardware experiment are implemented to prove the effectiveness of the proposed method. Hardware experiment is carried out on a tracked mobile robot. An omnidirectional vision is used to locate the robot in the surroundings. Forecast improvement of the proposed method is then discussed at the end.
Comparing Strategies to Prevent Stroke and Ischemic Heart Disease in the Tunisian Population: Markov Modeling Approach Using a Comprehensive Sensitivity Analysis Algorithm
Authors: Saidi Olfa , O’Flaherty Martin , Zoghlami Nada , Malouche Dhafer , Capewell Simon , Critchley Julia A. , Bandosz Piotr , Ben Romdhane Habiba , Guzman Castillo Maria
Published: January 2019

Background. Mathematical models offer the potential to analyze and compare the effectiveness of very different interventions to prevent future cardiovascular disease. We developed a comprehensive Markov model to assess the impact of three interventions to reduce ischemic heart diseases (IHD) and stroke deaths: (i) improved medical treatments in acute phase, (ii) secondary prevention by increasing the uptake of statins, (iii) primary prevention using health promotion to reduce dietary salt consumption. Methods. We developed and validated a Markov model for the Tunisian population aged 35–94 years old over a 20-year time horizon. We compared the impact of specific treatments for stroke, lifestyle, and primary prevention on both IHD and stroke deaths. We then undertook extensive sensitivity analyses using both a probabilistic multivariate approach and simple linear regression (metamodeling). Results. The model forecast a dramatic mortality rise, with 111,134 IHD and stroke deaths (95% CI 106567 to 115048) predicted in 2025 in Tunisia. The salt reduction offered the potentially most powerful preventive intervention that might reduce IHD and stroke deaths by 27% (−30240 [−30580 to −29900]) compared with 1% for medical strategies and 3% for secondary prevention. The metamodeling highlighted that the initial development of a minor stroke substantially increased the subsequent probability of a fatal stroke or IHD death. Conclusions. The primary prevention of cardiovascular disease via a reduction in dietary salt consumption appeared much more effective than secondary or tertiary prevention approaches. Our simple but comprehensive model offers a potentially attractive methodological approach that might now be extended and replicated in other contexts and populations.
Nanoenabled Bioseparations: Current Developments and Future Prospects
Authors: Fahmy Sherif Ashraf , Alawak Mohamad , Brüßler Jana , Bakowsky Udo , El Sayed Mayyada M. H.
Published: January 2019

The use of nanomaterials in bioseparations has been recently introduced to overcome the drawbacks of the conventional methods. Different forms of nanomaterials, particularly magnetic nanoparticles (MNPs), carbon nanotubes (CNTs), casted nanoporous membranes, and electrospun nanofiber membranes were utilized in biological separation for the aim of production of different biomolecules such as proteins, amino acids, nucleic acids, and enzymes. This paper critically reviews the state-of-the-art efforts undertaken in this regard, with emphasis on the synthesis and performance evaluation of each nanoform. Challenges and future prospects in developing nanoenabled bioseparations are also discussed, for the purpose of highlighting potential advances in the synthesis and fabrication of novel nanomaterials as well as in the design of efficient nanoenabled processes for separating a wide spectrum of biomolecules.
Disease-Modifying Effects of Long-Term and Continuous Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Spondyloarthritis
Authors: Wong Rebecca S. Y.
Published: January 2019

Spondyloarthritis or spondyloarthropathy (SpA) is a group of related rheumatic disorders, which presents with axial and nonaxial features, affecting structures within the musculoskeletal system, as well as other bodily systems. Both pharmacological and nonpharmacological therapeutic options are available for SpA. For decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as the first-line drugs to treat the disease. Research has shown that other than pain relief, NSAIDs have disease-modifying effects in SpA. However, to achieve these effects, continuous and/or long-term NSAID use is usually required. This review will give an overview of SpA, discuss NSAIDs and their disease-modifying effects in SpA, and highlight some of the important adverse effects of long-term and continuous NSAID use, particularly those related to the gastrointestinal, renal, and cardiovascular systems.
Antimutagenic and Synergistic Cytotoxic Effect of Cisplatin and Honey Bee Venom on 4T1 Invasive Mammary Carcinoma Cell Line
Authors: Shiassi Arani Faranak , Karimzadeh Latifeh , Ghafoori Seyed Mohammad , Nabiuni Mohammad
Published: January 2019

Introduction. Honey bee venom (HBV) has various biological activities such as the inhibitory effect on several types of cancer. Cisplatin is an old and potent drug to treat most of the cancers. Our aim in the present study was to determine antimutagenic and cytotoxic effects of HBV on mammary carcinoma, exclusively and in combination with cisplatin. Methods. In this study, 4T1 cell line was cultured in RPMI-1640 with 10% fetal bovine serum (FBS), at 37°C in humidified CO2 incubator. The cell viabilities were examined by the MTT assay. Also, HBV was screened‏ for its antimutagenic activity via the Ames test. The results were assessed by SPSS software version 19 and one-way ANOVA method considering p<0.05 level of significance. Results. The results showed that 6 mg/ml of HBV, 20 μg/ml of cisplatin, and 6 mg/ml HBV with 10 μg/ml cisplatin could induce approximately 50% of 4T1 cell death. The concentration 7 mg/ml of HBV with of 62.76% inhibitory rate showed the highest antimutagenic activity in comparison with other treatment groups. Conclusions. The MTT assay demonstrated that HBV and cisplatin could cause cell death in a dose-dependent manner. The cytotoxic effect of cisplatin also promoted by HBV. Ames test outcomes indicated that HBV could act as a significant mutagenic agent. The antimutagenic activity of HBV was increased considerably in the presence of S9 mix. Therefore, our findings have revealed that HBV can enhance the cytotoxic effect of cisplatin drug and its cancer-preventing effects.
An Extension of Totohasina’s Normalization Theory of Quality Measures of Association Rules
Authors: Armand  , Totohasina André , Feno Daniel Rajaonasy
Published: January 2019

In the context of binary data mining, for unifying view on probabilistic quality measures of association rules, Totohasina’s theory of normalization of quality measures of association rules primarily based on affine homeomorphism presents some drawbacks. Indeed, it cannot normalize some interestingness measures which are explained below. This paper presents an extension of it, as a new normalization method based on proper homographic homeomorphism that appears most consequent.
Nanoclays in Food and Beverage Packaging
Authors: Bumbudsanpharoke Nattinee , Ko Seonghyuk
Published: January 2019

In this study, we present and discuss the technical benefits of using nanoclays as a promising property enhancer in organic polymers for food and beverage packaging. The incorporation of nanoclays can improve the thermal, mechanical, and barrier properties of a host polymer. Both natural hydrophilic and modified organophilic nanoclays provide unique characteristics to the host polymer depending on the selected applications. Besides the advantage of polymer reinforcement, various novel applications of nanoclays in food packaging have been suggested recently, such as control and release for active ingredients, antimicrobial agent, and carrier for the colorimetric indicator system. The existing migration studies discussing the transition from plastic to nanoclay packaging revealed that the diffused level of aluminum and silicon in the nanoclay packaging are within the limitation proposed in Council Directive 90/128/EEC (1990). Therefore, until now, there is no safety restriction in the use of clay nanocomposite films in food packaging applications.
Robust Optimum Design of Multiple Tuned Mass Dampers for Vibration Control in Buildings Subjected to Seismic Excitation
Authors: Vellar Luciara Silva , Ontiveros-Pérez Sergio Pastor , Miguel Letícia Fleck Fadel , Fadel Miguel Leandro Fleck
Published: January 2019

Passive energy devices are well known due to their performance for vibration control in buildings subjected to dynamic excitations. Tuned mass damper (TMD) is one of the oldest passive devices, and it has been very much used for vibration control in buildings around the world. However, the best parameters in terms of stiffness and damping and the best position of the TMD to be installed in the structure are an area that has been studied in recent years, seeking optimal designs of such device for attenuation of structural dynamic response. Thus, in this work, a new methodology for simultaneous optimization of parameters and positions of multiple tuned mass dampers (MTMDs) in buildings subjected to earthquakes is proposed. It is important to highlight that the proposed optimization methodology considers uncertainties present in the structural parameters, in the dynamic load, and also in the MTMD design with the aim of obtaining a robust design; that is, a MTMD design that is not sensitive to the variations of the parameters involved in the dynamic behavior of the structure. For illustration purposes, the proposed methodology is applied in a 10‐story building, confirming its effectiveness. Thus, it is believed that the proposed methodology can be used as a promising tool for MTMD design.
Cervical Cancer–Instructed Stromal Fibroblasts Enhance IL23 Expression in Dendritic Cells to Support Expansion of Th17 Cells
Authors: Walch-Rückheim Barbara , Ströder Russalina , Theobald Laura , Pahne-Zeppenfeld Jennifer , Hegde Subramanya , Kim Yoo-Jin , Bohle Rainer Maria , Juhasz-Böss Ingolf , Solomayer Erich-Franz , Smola Sigrun
Published: January 2019

Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV-transformed cells actively instruct their microenvironment, promoting chronic inflammation and cancer progression. We previously demonstrated that cervical cancer cells contribute to Th17 cell recruitment, a cell type with protumorigenic properties. In this study, we analyzed the expression of the Th17-promoting cytokine IL23 in the cervical cancer micromilieu and found CD83+ mature dendritic cells (mDC) coexpressing IL23 in the stroma of cervical squamous cell carcinomas in situ. This expression of IL23 correlated with stromal Th17 cells, advanced tumor stage, lymph node metastasis, and cervical cancer recurrence. Cocultures of cervical cancer–instructed mDCs and cervical fibroblasts led to potent protumorigenic expansion of Th17 cells in vitro but failed to induce antitumor Th1 differentiation. Correspondingly, cervical cancer–instructed fibroblasts increased IL23 production in cocultured cervical cancer–instructed mDCs, which mediated subsequent Th17 cell expansion. In contrast, production of the Th1-polarizing cytokine IL12 in the cancer-instructed mDCs was strongly reduced. This differential IL23 and IL12 regulation was the consequence of an increased expression of the IL23 subunits IL23p19 and IL12p40 but decreased expression of the IL12 subunit IL12p35 in cervical cancer–instructed mDCs. Cervical cancer cell–derived IL6 directly suppressed IL12p35 in mDCs but indirectly induced IL23 expression in fibroblast-primed mDCs via CAAT/enhancer-binding protein β (C/EBPβ)–dependent induction of IL1β. In summary, our study defines a mechanism by which the cervical cancer micromilieu supports IL23-mediated Th17 expansion associated with cancer progression.

Significance:

Cervical cancer cells differentially regulate IL23 and IL12 in DC fibroblast cocultures in an IL6/C/EBPβ/IL1β-dependent manner, thereby supporting the expansion of Th17 cells during cancer progression.
CCR2-Dependent Recruitment of Tregs and Monocytes Following Radiotherapy Is Associated with TNFα-Mediated Resistance
Authors: Mondini Michele , Loyher Pierre-Louis , Hamon Pauline , Gerbé de Thoré Marine , Laviron Marie , Berthelot Kevin , Clémenson Céline , Salomon Benoit L. , Combadière Christophe , Deutsch Eric , Boissonnas Alexandre
Published: January 2019

Radiotherapy (RT) represents one of the main anticancer approaches for the treatment of solid tumors. Beyond the expected direct effects of RT on tumor cells, evidence supporting the importance of an immune response to RT is growing. The balance between RT-mediated immunogenic and tolerogenic activity is ill-defined and deserves more attention. Herein, a murine model of head and neck squamous cell carcinoma was used to demonstrate that RT upregulated CCL2 chemokine production in tumor cells, leading to a CCR2-dependent accumulation of tumor necrosis factor alpha (TNFα)-producing monocytes and CCR2+ regulatory T cells (Treg). This corecruitment was associated with a TNFα-dependent activation of Tregs, dampening the efficacy of RT. Our results highlight an unexpected cross-talk between innate and adaptive immune system components and indicate CCL2/CCR2 and TNFα as potential clinical candidates to counterbalance the radioprotective action of monocyte-derived cells and Tregs, paving the way for potent combined radioimmunotherapies.
Iron Chelation as Novel Treatment for Interstitial Cystitis
Authors: Hagn Georg , Westhofen Robert , Burkovskiy Ian , Holbein Bruce , Zhou Juan , Lehmann Christian
Published: January 2019

Interstitial cystitis (IC) is a highly prevalent debilitating disease, with its cardinal symptoms being severe pain, urinary urgency and frequency. The associated pain may eventually lead as a last resort to removal of the bladder. Though the initial trigger for IC remains largely unknown, we propose novel iron chelators as a possible new treatment for this disease. Iron is a mandatory component for the generation of reactive oxygen species (ROS). A substantial decrease in ROS production and thus inflammation can be achieved by effectively sequestering host iron, which we believe may improve outcome and quality of life in IC patients. Novel iron chelators could be used via the intravesical route to reduce or attenuate inflammation by effectively sequestering host iron, thus preventing the production of ROS via the Fenton and Haber-Weiss reactions.
ESPE and PES International Survey of Centers and Clinicians Delivering Specialist Care for Children and Adolescents with Gender Dysphoria
Authors: Skordis Nicos , Butler Gary , de Vries Martine C. , Main Katharina , Hannema Sabine E.
Published: January 2019

Background/Aims: Increasing numbers of children and adolescents seek medical care because they experience incongruence between their physical sex and their gender identity. Methods: The ESPE working group on gender dysphoria (GD) undertook a survey to investigate the structure and the type of medical care in centers that offer specialist care for transgender adolescents. Results: The personnel of each center varied from country to country, and a nationally organized network or plan for managing GD did not exist in all centers. The majority of young people were transitioning from female to male, and the number of new referrals increased remarkably during the past 3 years. Almost all centers follow the guidelines issued by the Endocrine Society and World Professional Association for Transgender Health. GnRH analogues were used as the initial treatment in the majority of the centers. The age from which adolescents are treated with gender-affirming hormones varied between centers. Several legal restrictions that concern or influence the treatment of children and adolescents with GD were finally addressed. Conclusion: This first international survey examining the variations in availability and provisions of services for children and adolescents with GD serves as a starting block for further dialogue and future studies.
Impact of Different Pharmacotherapies on Long-Term Outcomes in Patients with Electrical Storm
Authors: Schupp Tobias , Behnes Michael , Ellguth Dominik , Müller Julian , Reiser Linda , Bollow Armin , Taton Gabriel , Reichelt Thomas , Engelke Niko , Kim Seung-hyun , Nienaber Christoph , Akin Muharrem , Mashayekhi Kambis , Bertsch Thomas , Borggrefe Martin , Akin Ibrahim
Published: January 2019

Objective: The study sought to assess the long-term prognostic impact of different pharmacotherapies, including angiotensin-converting enzyme inhibitor-inhibitor/angiotensin receptor blocker (ACEi/ARB), statins, and amiodarone in patients with electrical storm (ES). Background: Data regarding the outcome of patients with ES is limited. Methods: Consecutive patients with ES from 2002 to 2016 were included. Patients on ACEi/ARB were compared to patients without ACEi/ARB, respectively, for statin and amiodarone therapy. The primary prognostic endpoint was all-cause mortality at 4 years. Secondary endpoints comprised ES recurrences, rehospitalization, and major adverse cardiac events (MACE) at 4 years. Kaplan-Meier survival curves and multivariable Cox regression analyses were applied. Results: A total of 84 consecutive patients surviving episodes of ES was included. Beta-blocker was given in 95%, ACEi/ARB in 80%, statin in 60%, and amiodarone in 54%. ACEi/ARB patients were associated with improved all-cause mortality at 4 years (mortality rate 34 vs. 65%, log rank p = 0.018; HR 0.428; 95% CI 0.208–0.881; p = 0.021), as well as improved freedom from MACE. In contrast, statin and amiodarone therapy had no impact on long-term outcomes in ES patients. Conclusion: ACEi/ARB therapy is associated with improved survival and MACE in patients with ES, whereas statins and amiodarone therapy had no impact on long-term prognostic endpoints.
Humour et subjectivités: retour critique sur le film Intouchables
Authors: Pele Antonio
Published: January 2019

O artigo procura entender algumas das bases socioculturais que presidem a construção das relações entre os dois personagens principais do filme Os Intocáveis. Essa ficção nos permitirá identificar os códigos implícitos que definem certas subjetividades da sociedade francesa atual. Ao estudar o cruzamento da esfera pública com a privada, e inversamente, podemos ver como são construídos processos de assimialção e de reprodução de uma cultura específica. Assim, nosso objetivo consiste em mostrar como a análise dessas intersecções ocultas pode revelar algumas potencialidades críticas e políticas.
A sociologia econômica de Bourdieu: entrevista com Frédéric Lebaron
Authors: Candido Silvio Eduardo Alvarez , Soule Fernanda Veríssimo , Assis Karina Gomes
Published: January 2019

Entrevista com Frédéric Lebaron sobre a sociologia econômica de Pierre Bourdieu.
O efeito da família no comportamento financeiro de adolescentes em escolas públicas
Authors: Dal Magro Cristian Baú , Gorla Marcello Christiano , Silva Tarcísio Pedro da , Hein Nelson
Published: January 2019

O estudo analisa o efeito da interação da família no comportamento financeiro de adolescentes em escolas da rede pública de ensino. A educação financeira e suas consequências no comportamento futuro de adultos têm origem na infância e adolescência. Foi aplicado questionário em cerca de 1.900 alunos do ensino médio de 14 escolas públicas na região Sul do país. Os resultados indicam que o comportamento típico de falta de controle dos gastos e a baixa propensão à poupança estão relacionados com uma menor discussão do tema em família. De modo geral, a família exerce importante papel em disseminar o conhecimento financeiro inicial, ou este se dá em situações cotidianas.
Caso para ensino: o processo de escolhas metodológicas em uma abordagem quantitativa
Authors: Lana Jeferson , Partyka Raul Beal , Alberton Anete , Marcon Rosilene
Published: January 2019

O caso para ensino trata do processo de amadurecimento de um problema de pesquisa em um programa de mestrado em Administração e Contabilidade, no paradigma positivista, em uma abordagem quantitativa. O caso adota uma narrativa e diálogos típicos entre um aluno de mestrado e seu orientador e professores, para expor os pontos de tensão e escolhas que emergem no primeiro ano de um típico programa de mestrado na área. O caso permite ao aluno conhecer uma típica interação no mestrado na área e refletir sobre a sequência de escolhas de técnicas estatísticas específicas. O caso de ensino é sugerido para disciplinas como metodologia de pesquisa, métodos quantitativos, seminários de dissertação no mestrado, e também para iniciação científica.
Os estudos de Boris Eikhenbaum sobre a obra de Mikhail Lérmontov
Authors: Pinto Pedro Augusto , Francisco Júnior Mario Ramos
Published: January 2019

O presente artigo analisa alguns aspectos dos estudos empreendidos pelo crítico russo Boris Eikhenbaum sobre a obra de Mikhail Lérmontov – mais precisamente, a monografia de 1924, Liérmontov – Ópyt Istóriko-Literatúrnoi Otsiénki (“Lérmontov – Uma tentativa de avaliação histórico-literária”) e o artigo de 1941, Literatúrnaia pozítsiia Liérmontova (“A posição literária de Lérmontov”). Dado que a monografia de 1924 pertence à fase propriamente formalista de Eikhenbaum – quando ele buscava afirmar, com intenções claramente polêmicas, a autonomia constitutiva da obra de arte tanto em relação ao seu contexto quanto em relação à personalidade de seu autor –, e que o artigo de 1941, por sua vez, já consta no rol de suas obras tardias, nas quais a figura do autor ressurge como mediação entre a obra e o contexto histórico, procuraremos comparar os dois textos e, a despeito de sua flagrante distinção metodológica, observar como a conjunção entre as duas abordagens pode colaborar para um estudo integrado da obra de Lérmontov, em que constem tanto a análise textual quanto a contextualização histórica e em consonância com a moderna História da Cultura.
Unmet need for assistance with activities of daily life among older adults in Brazil
Authors: Andrade Tania Bof de , Andrade Fabiola Bof de
Published: January 2019

OBJECTIVE: To estimate the proportion of unmet need for personal assistance for basic and instrumental activities of daily life and to evaluate socioeconomic inequalities related to the unmet need among community-dwelling Brazilian older adults. METHODS: This was a cross-sectional study with data from the last National Health Survey in Brazil. Unmet need was considered as the presence of at least one unmet need for basic or instrumental activities of daily life among individuals reporting the need for assistance. Logistic regression models were used to assess the correlates and probabilities of unmet need. RESULTS: The proportion of unmet need was 18% and 7.1% for basic and instrumental activities of daily life, respectively. Unmet need was significantly related to living arrangements and socioeconomic status. Individuals in the first quintile of wealth status had about 50% higher probability of having an unmet need. A family member was the most prevalent type of caregiver. CONCLUSIONS: Long-term care policy is needed to reduce the proportion of unmet need, especially among socioeconomically disadvantaged groups. Future studies should address the availability, training, and remuneration of caregivers, as those are an indispensable labor force in an aging society
Factors associated with frailty in older adults
Authors: Fhon Jack Roberto Silva , Rodrigues Rosalina Aparecida Partezani , Santos Jair Lício Ferreira , Diniz Marina Aleixo , Santos Emanuella Barros dos , Almeida Vanessa Costa , Giacomini Suelen Borelli Lima
Published: January 2019

OBJECTIVE: To determine the demographic and health factors related to the frailty syndrome in older adults. METHODS: This is a longitudinal quantitative study carried out with 262 older adults aged 65 years and older, of both sexes, living at home. Data collection was carried out in Period 1 between October 2007 and February 2008, and in Period 2 between July and December 2013. For data collection, we used the sociodemographic profile instrument, the Edmonton Frail Scale, the Mini-Mental State Examination, the number of falls in the last 12 months, the number of self-reported diseases and used drugs, the Functional Independence Measure, and the Lawton and Brody Scale. We used descriptive statistics for data analysis, in the comparison of the means between periods, the nonparametric Wilcoxon test, and the method of Generalized Estimating Equations, which is considered an extension of the Generalized Linear Models with p ≤ 0.05. RESULTS: Of the 515 participants, 262 completed the follow-up, with a predominance of females, older individuals, and those who had no partner; there was an increase in frail older adults. In the Generalized Estimating Equations analysis, frailty score was related to sociodemographic (increase in age, no partner, and low education level) and health variables (more diseases, drugs, falls, and decrease in functional capacity). There was an association between the variables of age (older), marital status (no partner), and loss of functional capacity. CONCLUSIONS: Frailty syndrome was associated with increasing age, having no partner, and decreased functional capacity over time, and investments are required to prevent this syndrome and promote quality in aging.
How Rising Powers Create Governance Gaps: The Case of Export Credit and the Environment
Authors: Hopewell Kristen
Published: January 2019

This article analyzes how rising powers are affecting an important area of global governance at the intersection of trade and environment: export credit. State-backed export credit agencies (ECAs) play a major role in financing large infrastructure and energy projects, particularly in developing countries. Many of these projects carry significant environmental implications, yet there has been little scholarly attention to their governance. Since the 1990s, global governance of the environmental practices of ECAs has been progressively expanded and strengthened via the OECD Arrangement on export credit and Common Approaches for environmental and social due diligence. Recently, however, there has been a dramatic increase in export credit provision by rising powers, such as India and China, who are not members of the OECD nor subject to the Arrangement or Common Approaches. In this article, I argue that existing governance mechanisms have not caught up with the rapidly changing landscape of export credit. Drawing on the case of India’s financing for the Rampal coal-fired power plant in Bangladesh, I show that the problem of environmental governance for export credit increasingly extends beyond the advanced-industrialized states of the OECD. The failure to cover the large and growing volume of export credit provided by the emerging powers represents a major gap in the established system of environmental governance for export credit.
Impact of gamma irradiation on tissues of the mud crab, Scylla serrata (Forskål, 1775) (Decapoda, Portunidae) — electron microscopic study and DNA comet assay
Authors: Keethadath Arshad , Kappalli Sudha , Gayathri N. , Thomas Derin M. , Anilkumar Gopinathan
Published: January 2019

Radiopreservation using gamma radiation is widely in use as a safe method for extending the shelf life of shellfish. This study explored the consequences of different doses of gamma radiation (0.5 kGy, 1.0 kGy and 2.0 kGy) on various tissues of Scylla serrata at cellular and nuclear level, with the aid of electron microscopy and DNA comet assay. The highly radio exposed (2.0 kGy) pyloric muscles showed a reduction in sarcomere length, disordered organization with expanded gap between adjacent myofibrils, ruptured sarcotubular system, mitochondrial swelling with crushed cristae, significant increase in nucleus size coupled with less dense nucleoplasm, etc. Comet assay on tissues such as muscle, hepatopancreas and testis irradiated with 2.0 kGy radiation also revealed a significant degree of nuclear damage by gamma irradiation in a dose-dependent manner. The tail length of the comet showed a tissue-specific tolerance level. The present study clarified the precise dose of irradiation as 1.0 kGy and the results can be relevant for commercial purposes to qualitatively categorize the irradiated crabs.
Panulirus echinatus population in the Brazilian oceanic ecosystem Rocas Atoll
Authors: Gaeta Juliana , Cruz Raúl
Published: January 2019

In Rocas Atoll (03°51′S 033°48′W) a most abundant population of Panulirus echinatus Smith, 1869 was observed during free dives. Numbers of males and females were almost the same, with an overall sex ratio M : F = 1.1. In addition, males are larger than females, with a mean male carapace length (CL) of 92.6 ± 1.8 mm, while the female mean CL was 72.7 ± 1.0 mm and for both sex combined the mean CL was 83.1 ± 1.4 mm. The percentage of females breeding, i.e., with a spermatophore mass or eggs, was 75.1%. More information is needed to better understand the fluctuation in densities over a year cycle, the reproduction period, and differences in CL between males and females, as well as other aspects of the biology of this species. The present work and future information could help to formulate fisheries policies aimed at protecting P. echinatus stocks.
Forficatocaris odeteae n. sp., a new Parastenocarididae (Copepoda, Harpacticoida) from a high-altitude pond in Minas Gerais state, Brazil
Authors: Moreira Raquel A. , Eskinazi-Sant’Anna Eneida M. , Previattelli Daniel
Published: January 2019

A new species of harpacticoid copepod, genus Forficatocaris (F. odeteae n. sp.) is described from a high-altitude pond at the Itacolomi National Park near Ouro Preto city, Minas Gerais state, Brazil. The main characters distinguishing the new species from F. affinis Dussart, 1983 and F. lilianae Noodt, 1972 are: (i) distal portion of exopod 1 of male leg 4 with stout spinules; (ii) male leg 5 lateral spine stout and with blunt apex; (iii) endopod of leg 4 curved outwards, but “c” shaped (not forming a straight angle); (iv) female with dorsal spinule row on anal somite larger than in congeners, ventral ornaments smaller and less numerous; and (v) the shape of the modified spine located at the leg 1 endopod 1 of the male; and (vi) the spine of leg 5 in males and females.
From Italian Pushbacks to Libyan Pullbacks: Is Hirsi 2.0 in the Making in Strasbourg?
Authors: Pijnenburg Annick
Published: January 2019

This article discusses the application that was recently lodged with the European Court of Human Rights alleging that Italy is responsible for its involvement in pullbacks by the Libyan coast guard. It places the case in the wider context of migration control policies and the Hirsi case in particular. The article examines different pullback scenarios which feature in the application lodged with the Court, and discusses different ways in which the Court can address the issues raised. The analysis focuses particularly on the question whether the Court is likely to find that Italy exercises jurisdiction and whether Italy could incur derived responsibility for its involvement in the pullbacks. The article concludes by suggesting that holding Italy responsible would require the Court to move beyond established precedent in its case-law. Although this is a move which can be difficult to make given the political tide in Europe, it would not be the first time that the Court takes its case-law, and thereby human rights protection, a step further.