bluuebunny/crossref_metadata_2025 huggingface dataset:
A Low-Cost Automated Test Column to Estimate Soil Hydraulic Characteristics in Unsaturated Porous Media
Authors: Salas-García J. , Garfias J. , Martel R. , Bibiano-Cruz L.
Published: January 2017

The estimation of soil hydraulic properties in the vadose zone has some issues, such as accuracy, acquisition time, and cost. In this study, an inexpensive automated test column (ATC) was developed to characterize water flow in a homogeneous unsaturated porous medium by the simultaneous estimation of three hydraulic state variables: water content, matric potential, and water flow rates. The ATC includes five electrical resistance probes, two minitensiometers, and a drop counter, which were tested with infiltration tests using the Hydrus-1D model. The results show that calibrations of electrical resistance probes reasonably match with similar studies, and the maximum error of calibration of the tensiometers was 4.6% with respect to the full range. Data measured by the drop counter installed in the ATC exhibited a high consistency with the electrical resistance probes, which provides an independent verification of the model and indicates an evaluation of the water mass balance. The study results show good performance of the model against the infiltration tests, which suggests a robustness of the methodology developed in this study. An extension to the applicability of this system could be successfully used in low-budget projects in large-scale field experiments, which may be correlated with resistivity changes.
Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma
Authors: Almazán-Moga Ana , Zarzosa Patricia , Vidal Isaac , Molist Carla , Giralt Irina , Navarro Natalia , Soriano Aroa , Segura Miguel F. , Alfranca Arantza , Garcia-Castro Javier , Sánchez de Toledo José , Roma Josep , Gallego Soledad
Published: January 2017

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and can be divided into two main subtypes: embryonal (eRMS) and alveolar (aRMS). Among the cellular heterogeneity of tumors, the existence of a small fraction of cells called cancer stem cells (CSC), thought to be responsible for the onset and propagation of cancer, has been demonstrated in some neoplasia. Although the existence of CSC has been reported for eRMS, their existence in aRMS, the most malignant subtype, has not been demonstrated to date. Given the lack of suitable markers to identify this subpopulation in aRMS, we used cancer stem cell-enriched supracellular structures (spheres and holoclones) to study this subpopulation. This strategy allowed us to demonstrate the capacity of both aRMS and eRMS cells to form these structures and retain self-renewal capacity. Furthermore, cells contained in spheres and holoclones showed significant Hedgehog pathway induction, the inhibition of which (pharmacologic or genetic) impairs the formation of both holoclones and spheres. Our findings point to a crucial role of this pathway in the maintenance of these structures and suggest that Hedgehog pathway targeting in CSC may have great potential in preventing local relapses and metastases.
Cloud-Based DDoS HTTP Attack Detection Using Covariance Matrix Approach
Authors: Aborujilah Abdulaziz , Musa Shahrulniza
Published: January 2017

In this era of technology, cloud computing technology has become essential part of the IT services used the daily life. In this regard, website hosting services are gradually moving to the cloud. This adds new valued feature to the cloud-based websites and at the same time introduces new threats for such services. DDoS attack is one such serious threat. Covariance matrix approach is used in this article to detect such attacks. The results were encouraging, according to confusion matrix and ROC descriptors.
CEP Calculation Based on Weighted Bayesian Mixture Model
Authors: Zhang Shengdi , Duan Xiaojun , Li Chang , Peng Xiaojun , Zhang Qiang
Published: January 2017

CEP is an important accuracy index in the test evaluation for guidance weapon systems. As for the samples origin from diverse populations, which is a general case in the practice, traditional method with one population is inaccurate to give estimate directly. A weighted method considering the credibility of the prior information is proposed for Bayesian estimation algorithm and the weighted estimation of normal distribution parameters is provided. And the statistical diversity between the weighted and classical methods is quantified, and upper bound of the calculation errors caused by prior distortion is deduced for mixture of finite normal distributions. Taking the estimation of the dispersion of the guided weapon impact points as an example, the conclusion is drawn that our method is credible.
Causal Analysis of an Agent-Based Model of Human Behaviour
Authors: Kvassay Marcel , Krammer Peter , Hluchý Ladislav , Schneider Bernhard
Published: January 2017

This article investigates causal relationships leading to emergence in an agent-based model of human behaviour. A new method based on nonlinear structural causality is formulated and practically demonstrated. The method is based on the concept of acausal partitionof a model variable which quantifies the contribution of various factors to its numerical value. Causal partitions make it possible to judge the relative importance of contributing factors over crucial early periods in which the emergent behaviour of a system begins to form. They can also serve as the predictors of emergence. The time-evolution of their predictive power and its distribution among their components hint at the deeper causes of emergence and the possibilities to control it.
A Design of a New Column-Parallel Analog-to-Digital Converter Flash for Monolithic Active Pixel Sensor
Authors: Chakir Mostafa , Akhamal Hicham , Qjidaa Hassan
Published: January 2017

The CMOS Monolithic Active Pixel Sensor (MAPS) for the International Linear Collider (ILC) vertex detector (VXD) expresses stringent requirements on their analog readout electronics, specifically on the analog-to-digital converter (ADC). This paper concerns designing and optimizing a new architecture of a low power, high speed, and small-area 4-bit column-parallel ADC Flash. Later in this study, we propose to interpose an S/H block in the converter. This integration of S/H block increases the sensitiveness of the converter to the very small amplitude of the input signal from the sensor and provides a sufficient time to the converter to be able to code the input signal. This ADC is developed in 0.18 μm CMOS process with a pixel pitch of 35 μm. The proposed ADC responds to the constraints of power dissipation, size, and speed for the MAPS composed of a matrix of 64 rows and 48 columns where each column ADC covers a small area of 35 × 336.76 μm2. The proposed ADC consumes low power at a 1.8 V supply and 100 MS/s sampling rate with dynamic range of 125 mV. Its DNL and INL are 0.0812/−0.0787 LSB and 0.0811/−0.0787 LSB, respectively. Furthermore, this ADC achieves a high speed more than 5 GHz.
Considering the Specific Impact of Harsh Conditions and Oil Weathering on Diversity, Adaptation, and Activity of Hydrocarbon-Degrading Bacteria in Strategies of Bioremediation of Harsh Oily-Polluted Soils
Authors: Al Disi Zulfa , Jaoua Samir , Al-Thani Dhabia , Al-Meer Saeed , Zouari Nabil
Published: January 2017

Weathering processes change properties and composition of spilled oil, representing the main reason of failure of bioaugmentation strategies. Our purpose was to investigate the metabolic adaptation of hydrocarbon-degrading bacteria at harsh conditions to be considered to overcome the limitations of bioaugmentation strategies at harsh conditions. Polluted soils, exposed for prolonged periods to weathered oil in harsh soils and weather conditions, were used. Two types of enrichment cultures were employed using 5% and 10% oil or diesel as sole carbon sources with varying the mineral nitrogen sources and C/N ratios. The most effective isolates were obtained based on growth, tolerance to toxicity, and removal efficiency of diesel hydrocarbons. Activities of the newly isolated bacteria, in relation to the microenvironment from where they were isoalted and their interaction with the weathered oil, showed individual specific ability to adapt when exposed to such factors, to acquire metabolic potentialities. Among 39 isolates, ten identified ones by 16S rDNA genes similarities, including special two Pseudomonas isolates and one Citrobacter isolate, showed particularity of shifting hydrocarbon-degrading ability from short chain n-alkanes (n-C12–n-C16) to longer chain n-alkanes (n-C21–n-C25) and vice versa by alternating nitrogen source compositions and C/N ratios. This is shown for the first time.
The Effect of PEI and PVP-Stabilized Gold Nanoparticles on Equine Platelets Activation: Potential Application in Equine Regenerative Medicine
Authors: Hecold Mateusz , Buczkowska Roma , Mucha Aleksandra , Grzesiak Jakub , Rac-Rumijowska Olga , Teterycz Helena , Marycz Krzysztof
Published: January 2017

The aim of this work was to assess the effect of different stabilizing agents, for example, polyethylenimine (PEI) and polyvinylpyrrolidone (PVP), on gold nanoparticles (AuNPs) and their influence on equine platelet activation and release of particular growth factors. The gold nanoparticles were produced by chemical reduction of chloroauric acid. UV-Vis spectroscopy confirmed the presence of gold nanoparticles in investigated solutions. The AuNPs were incubated with whole blood at various concentrations. The morphology of platelets in PRP prepared from the blood incubated with AuNPs was characterized by scanning transmission electron microscopy, whereas the concentrations of growth factors and cytokines were evaluated by ELISA assays. The most promising results were obtained with equine platelets incubated with 5% AuNPs stabilized by PEI, which lead to secretion of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), and fibroblast growth factor 1 (FGF-1) and simultaneously cause decrease in concentration of interleukin-1 alpha (IL-1α). The qRT-PCR confirmed ELISA test results. The incubation with 5% AuNPs stabilized by PEI leads to upregulation of BMP-2 and VEGF transcripts of mRNA level and to downregulating expression of interleukin-6 (IL-6). Obtained data shed a promising light on gold nanoparticle application for future regenerative medicine application.
A Continuous 3D-Graphene Network to Overcome Threshold Issues and Contact Resistance in Thermally Conductive Graphene Nanocomposites
Authors: Conrado Federico , Pavese Matteo
Published: January 2017

In order to overcome thermal resistance issues in polymeric matrix composites, self-standing graphene aerogels were synthetized and infiltrated with an epoxy resin, in order to create conductive preferential pathways through which heat can be easily transported. These continuous highly thermally conductive 3D-structures show, due to the high interconnection degree of graphene flakes, enhanced transport properties. Two kinds of aerogels were investigated, obtained by hydrothermal synthesis (HS) and ice-templated direct freeze synthesis (DFS). Following HS method an isotropic structure is obtained, and following DFS method instead an anisotropic arrangement of graphene flakes results. The density of the structure can be tuned leading to a different amount of graphene inside the final composite. The residual oxygen, known to be detrimental to thermal properties, was removed by thermal treatment before the infiltration process. With 1,25 wt.% of graphene, using HS method, the thermal conductivity of the polymeric resin was increased by 80%, suggesting that this technique is a valid route to improve the thermal performance of graphene-based composites. When preferential orientation of the filler was present (DFS case), thermal conductivity was increased more than 25% with a graphene content of only 0,27 wt.%, demonstrating that oriented structures can further improve the thermal transport efficiency.
Optimization of Hydrothermal and Diluted Acid Pretreatments of TunisianLuffa cylindrica(L.) Fibers for 2G Bioethanol Production through the Cubic Central Composite Experimental Design CCD: Response Surface Methodology
Authors: Zaafouri Kaouther , Ziadi Manel , Ben Hassen-Trabelsi Aida , Mekni Sabrine , Aïssi Balkiss , Alaya Marwen , Bergaoui Latifa , Hamdi Moktar
Published: January 2017

This paper opens up a new issue dealing withLuffa cylindrica(LC) lignocellulosic biomass recovery in order to produce 2G bioethanol. LC fibers are composed of three principal fractions, namely,α-cellulose (45.80%  ± 1.3), hemicelluloses (20.76%  ± 0.3), and lignins (13.15%  ± 0.6). The optimization of LC fibers hydrothermal and diluted acid pretreatments duration and temperature were achieved through the cubic central composite experimental design CCD. The pretreatments optimization was monitored via the determination of reducing sugars. Then, the 2G bioethanol process feasibility was tested by means of three successive steps, namely, LC fibers hydrothermal pretreatment performed at 96°C during 54 minutes, enzymatic saccharification carried out by means of a commercial enzyme AP2, and the alcoholic fermentation fulfilled withSaccharomyces cerevisiae. LC fibers hydrothermal pretreatment liberated 33.55 g/kg of reducing sugars. Enzymatic hydrolysis allowed achieving 59.4 g/kg of reducing sugars. The conversion yield of reducing sugar to ethanol was 88.66%. After the distillation step, concentration of ethanol was 1.58% with a volumetric yield about 70%.
The Total Return Swap Pricing Model under Fuzzy Random Environments
Authors: Wu Liang , Wang Jun-tao , Liu Jie-fang , Zhuang Ya-ming
Published: January 2017

This paper models the jump amplitude and frequency of random parameters of asset value as a triangular fuzzy interval. In other words, we put forward a new double exponential jump diffusion model with fuzziness, express the parameters in terms of total return swap pricing, and derive a fuzzy form pricing formula for the total return swap. Following simulation, we find that the more the fuzziness in financial markets, the more the possibility of fuzzy credit spreads enlarging. On the other hand, when investors exhibit stronger subjective beliefs, fuzzy credit spreads diminish. Using fuzzy information and random analysis, one can consider more uncertain sources to explain how the asset price jump process works and the subjective judgment of investors in financial markets under a variety of fuzzy conditions. An appropriate price range will give investors more flexibility in making a choice.
Aberrant Phosphorylation of SMAD4 Thr277-Mediated USP9x–SMAD4 Interaction by Free Fatty Acids Promotes Breast Cancer Metastasis
Authors: Wu Yong , Yu Xiaoting , Yi Xianghua , Wu Ke , Dwabe Sami , Atefi Mohammad , Elshimali Yahya , Kemp Kevin T. , Bhat Kruttika , Haro Jesse , Sarkissyan Marianna , Vadgama Jaydutt V.
Published: January 2017

Obesity increases the risk of distant metastatic recurrence and reduces breast cancer survival. However, the mechanisms behind this pathology and identification of relevant therapeutic targets are poorly defined. Plasma free fatty acids (FFA) levels are elevated in obese individuals. Here we report that TGFβ transiently activates ERK and subsequently phosphorylates SMAD4 at Thr277, which facilitates a SMAD4–USP9x interaction, SMAD4 nuclear retention, and stimulates TGFβ/SMAD3–mediated transcription of Twist and Snail. USP9x inhibited the E3 ubiquitin-protein ligase TIF1γ from binding and monoubiquitinating SMAD4, hence maintaining the SMAD4 nuclear retention. FFA further facilitated TGFβ-induced ERK activation, SMAD4 phosphorylation, and nuclear retention, promoting TGFβ-dependent cancer progression. Inhibition of ERK and USP9x suppressed obesity-induced metastasis. In addition, clinical data indicated that phospho-ERK and -SMAD4 levels correlate with activated TGFβ signaling and metastasis in overweight/obese patient breast cancer specimens. Altogether, we demonstrate the vital interaction of USP9x and SMAD4 for governing TGFβ signaling and dyslipidemia-induced aberrant TGFβ activation during breast cancer metastasis. Cancer Res; 77(6); 1383–94. ©2017 AACR.
Therapeutic Efficacy of 4-1BB Costimulation Is Abrogated by PD-1 Blockade in a Model of Spontaneous B-cell Lymphoma
Authors: McKee Sara J. , Doff Brianna L. , Soon Megan S.F. , Mattarollo Stephen R.
Published: January 2017

Combinations of mAbs that target various components of T-cell activation/inhibition may work synergistically to improve antitumor immunity against cancer. In this study, we investigated the therapeutic potential of combining an anticancer vaccination strategy with antibodies targeting an immune stimulatory (4-1BB) and immune inhibitory (PD-1) receptor, in a preclinical model of spontaneously arising c-Myc–driven B-cell lymphoma. In Eμ-myc transgenic mice, we reveal that 4-1BB agonistic mAb treatment alone was sufficient to drive antitumor immunity and prevent disease progression in 70% of mice. When combined with an α-GalCer–loaded, irradiated tumor cell vaccine, 4-1BB mAb treatment led to increased expansion of effector CD8 T-cell populations and protection of long-term surviving mice against tumor rechallenge. Unexpectedly, PD-1 blockade did not provide therapeutic benefit. The T-cell–promoting effects and antitumor activity of 4-1BB mAb were diminished when used simultaneously with a PD-1–blocking mAb. This was associated with a rapid and dramatic reduction in effector CD8+ T-cell subsets in the presence of PD-1 blockade. These findings reveal that supporting T-cell activation therapeutically is effective for controlling B-cell lymphomas; however, caution is required when combining antibody-mediated modulation of both costimulatory and coinhibitory T-cell receptors. Cancer Immunol Res; 5(3); 191–7. ©2017 AACR.
Cables1 Inhibits Proliferation and Induces Senescence by Angiotensin II via a p21-Dependent Pathway in Human Umbilical Vein Endothelial Cells
Authors: Pu Zhongyue , Wang Yongshun , Liu Xinxin , Liu Jingjin , Cui Jinjin , Wang Yan , Lv Bo , Yu Bo
Published: January 2017

Cables1 (Cdk5 and Abl enzyme substrate 1) is a vital cell cycle regulator and a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Here, we report on the critical role of the Cables1/p21 pathway, which inhibits cell proliferation and induces cell senescence in human umbilical vein endothelial cells. Moreover, we confirmed that silencing of Cables1 promoted cell proliferation as well as increased resistance to angiotensin II-induced senescence, at least in part, by altering Cables1 activation. We further demonstrated that knockdown of p21 reverses Cables1-mediated cell growth inhibition and cell senescence. Taken together, these results suggest that the Cables1/p21 pathway has a strong effect on the induction of cell senescence and inhibition of cell growth, and acts as a novel regulatory mechanism in which p21 is probably one of several downstream effector molecules to mediate Cables1.
The Effect of Autologous Platelet-Rich Plasma on Bone Regeneration by Autologous Mesenchymal Stem Cells Loaded onto Allogeneic Cancellous Bone Granules
Authors: Joo Min Wook , Chung Seung Jae , Shin Seung Han , Chung Yang-Guk
Published: January 2017

To develop a clinically effective bone regeneration strategy, we compared bone regeneration using allogeneic cancellous bone granule scaffolds loaded with autologous bone marrow-derived mesenchymal stem cells (BM-MSC) with or without autologous platelet-rich plasma (PRP). Critical-sized segmental bone defects were made at the mid-shaft of both radiuses in 41 New Zealand White rabbits. Small-sized allogeneic cancellous bone granules (300-700 μm in diameter) loaded with BM-MSC were implanted on one side, and PRP was added. On the other side, autologous BM-MSC loaded onto allogeneic cancellous granules were grafted as a control. Bone regeneration was assessed by radiographic evaluation at 4, 8, and 16 weeks postimplantation and by micro-computed tomography (micro-CT) and histological evaluation of the retrieved specimens at 8 and 16 weeks. The experimental group did not show significantly higher bone quantity indices than the control group at any time point. Micro-CT analysis revealed that both groups had similar mean total volumes, surface areas, and other parameters at 8 and 16 weeks. Histological evaluation of 8- and 16-week specimens also showed a similar progression of new bone formation and maturation. In this experiment using a contralateral control group in the same individual, an initial single addition of PRP in allogeneic cancellous bone granules loaded with BM-MSC for critical-sized bone defects in the weight-bearing area did not induce a consequent difference in bone healing. Further research into the optimal preparation and application of PRP is necessary. Furthermore, studies involving a greater number of subjects and larger experimental animals could determine the clinical relevance of PRP treatment.
Energy Metabolism and Ageing in the Mouse: A Mini-Review
Authors: Azzu Vian , Valencak Teresa G.
Published: January 2017

The mouse has rapidly become the mammalian model organism of choice in ageing research due to its relatively short lifespan, the proximity of its genome and physiology to humans, and most importantly due to its genetic pliability and the availability of mutant strains. Mouse models have provided great insights into the ageing process, which in its broadest sense is the progressive decline of body functions over time. In this mini-review, we briefly cover the historical views on the link between ageing and metabolic rate, highlight genetically modified transgenic mouse models of extended lifespan, discuss endocrine pathways linked to senescence and ageing, and then examine pathways by which caloric restriction is postulated to result in longevity.
Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer
Authors: Wan Yue-Ping , Xi Ming , He Hui-Chan , Wan Song , Hua Wei , Zen Zhao-Chang , Liu Yuan-Ling , Zhou Yu-Lin , Mo Ru-Jun , Zhuo Yang-Jia , Luo Hong-Wei , Jiang Fu-Neng , Zhong Wei-De
Published: January 2017

Background: Novel molecular markers are important diagnostic tools for the assessment of cancer progression and evaluation of effectiveness of the treatment. SOX9, a key regulator of developmental processes, is overexpressed in various neoplasms, such as prostate, breast, and colorectal cancers. However, the utilization of SOX9 as a biomarker for other urological cancers has not yet been investigated. Methods: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the SOX9 protein expression was quantitated as immunoreactive scores in patients with renal cell carcinoma (RCC), bladder cancer (BCa), and penile cancer (PC). Results: In comparison with normal tissues, SOX9 protein expression was signiﬁcantly upregulated in RCC (p < 0.001) and BCa (p < 0.001), and significantly correlated with the advanced pathological grade (RCC: p = 0.023) and clinical stage (RCC: p = 0.022 and BCa: p = 0.046) of patients. Based on the mRNA level in the TCGA dataset, SOX9 was upregulated in RCC with gender (p = 0.027), advanced pathological grade (p = 0.003) and advanced clinical stage (p = 0.001). Kaplan-Meier survival curves revealed that RCC patients with high SOX9 levels had shorter survival (p < 0.001). Further, high SOX9 expression was an independent prognostic factor for RCC patients (hazard ratio 0.056, 95% confidence interval 0.607-1.184; p < 0.001). Conclusion: These findings suggest that SOX9 may play an important role in tumor progression of RCC and BCa and it may be used as a biomarker of this malignancy.
Impact of EGFR-Tyrosine Kinase Inhibitors on Postoperative Recurrent Non-Small-Cell Lung Cancer Harboring EGFR Mutations
Authors: Igawa Satoshi , Ryuge Shiichiro , Ichinoe Masaaki , Nakashima Hiroyasu , Otani Sakiko , Nakahara Yoshiro , Fukui Tomoya , Sasaki Jiichiro , Kubota Masaru , Katagiri Masato , Murakumo Yoshiki , Satoh Yukitoshi , Sato Yuichi , Masuda Noriyuki
Published: January 2017

Background: It is unclear whether there is a difference in the efficacy of treatment by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) between patients with postoperative recurrent non-small-cell lung cancer (NSCLC) and those with stage IV NSCLC harboring EGFR mutations. Patients and Methods: The records of NSCLC patients harboring EGFR mutations who were treated with gefitinib or erlotinib were retrospectively reviewed, and the treatment outcomes were evaluated. Moreover, we performed an immunohistochemical analysis of PD-L1 expression in tumor lesions of the postoperative recurrence group. Results: In 205 patients, both the progression-free survival (PFS) time (9.4 vs. 16.9 months) and the median survival time (24.7 vs. 37.4 months) were significantly longer in the postoperative group than in the stage IV group. Additionally, multivariate analysis identified that postoperative recurrence was an independent predictor of PFS and overall survival, as were performance status and smoking status. The PFS durations were 15.7 and 16.6 months for the high- and low-PD-L1 expression groups, respectively, and no significant difference was observed (P = 0.73). Conclusions: The findings of this study provide a valuable rationale for considering postoperative recurrence as a predictive factor for favorable PFS and overall survival in patients with NSCLC harboring activating EGFR mutations who receive EGFR-TKIs.
Efficacy of Whole-Lung Lavage in Pulmonary Alveolar Proteinosis: A Multicenter International Study of GELF
Authors: Gay Pierre , Wallaert Benoit , Nowak Stefan , Yserbyt Jonas , Anevlavis Stavros , Hermant Christophe , Lovis Alban , Menard Olivier , Maitre Bernard , Vandemoortele Thomas , Dutau Hervé , Briault Amandine , Bourdin Arnaud , Vergnon Jean-Michel , Froudarakis Marios E. ,   Groupe d''Endoscopie Thoracique de Langue Française
Published: January 2017

Background: New therapies have emerged in the treatment of pulmonary alveolar proteinosis (PAP) and, therefore, there is a real need to evaluate the efficacy of whole-lung lavage (WLL) in this rare disease. Objectives: The aim of this study was to assess the efficacy of WLL in patients with PAP. Methods: We included 33 patients from 12 centers, which are members of the French-Speaking Thoracic Endoscopy Group, for analysis. Data collection concerned patients and disease characteristics, pulmonary function tests (PFTs) and technical information on the procedure. Results: The median age of the patients was 44 years (range 13-77). There were 23 (71.9%) patients with respiratory insufficiency at presentation. All patients underwent WLL by general anesthesia and selective lung ventilation, except 1 who underwent awake flexible bronchoscopy. We noted differences in the technique, as 12 (36.36%) patients had percussion during the procedure and only 4 (12.1%) patients underwent 2-lung lavage during 1 anesthesia. A median of 12 L was used to perform WLL (1.0-40 L). Complications occurred in 11 (33.3%) patients, and 18 (56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in any PFT parameters studied, except for PaO2, which was significantly improved by 6.375 mm Hg (p = 0.0213) after the procedure compared to before. Conclusions: Although the application of the WLL technique was variable, overall, it significantly improved patients' short-term respiratory condition by improving PaO2. However, a long-term effect needs to be confirmed, as many of our patients relapsed.
Dançarinos de quadrilha junina: um divertimento que é trabalho?
Authors: Silva Natália Bezerra da , Velôso Thelma Maria Grisi , Pinto Francinaldo Do Monte
Published: January 2017

Nos festejos juninos de Campina Grande, PB, conhecidos como “O maior São João do mundo”, as quadrilhas juninas são consideradas um grande ícone da festa. A partir de uma pesquisa realizada com dançarinos de quadrilha dessa cidade, nos ocuparemos, neste artigo, das representações sociais que são construídas sobre essa atividade. Foram realizadas, além da observação participante, vinte entrevistas semiestruturadas com dançarinos de ambos os sexos, das quadrilhas Arraial da Felicidade e Mistura Gostosa. A análise dos dados, operada pelo método hermenêutico-dialético, evidenciou que os dançarinos de quadrilhas juninas constroem diferentes representações sobre essa atividade: divertimento, lazer, prazer, responsabilidade e trabalho. Por fim, observou-se que os entrevistados constroem um discurso que enfatiza os efeitos positivos dessa atividade, o reconhecimento social, o entrosamento coletivo e a realização pessoal.
The Long Noncoding RNA Landscape of the Ischemic Human Left Ventricle
Authors: Saddic Louis A. , Sigurdsson Martin I. , Chang Tzuu-Wang , Mazaika Erica , Heydarpour Mahyar , Shernan Stanton K. , Seidman Christine E. , Seidman Jon G. , Aranki Sary F. , Body Simon C. , Muehlschlegel Jochen D.
Published: January 2017

Background—

The discovery of functional classes of long noncoding RNAs (lncRNAs) has expanded our understanding of the variety of RNA species that exist in cells. In the heart, lncRNAs have been implicated in the regulation of development, ischemic and dilated cardiomyopathy, and myocardial infarction. Nevertheless, there is a limited description of expression profiles for these transcripts in human subjects.

Methods and Results—

We obtained left ventricular tissue from human patients undergoing cardiac surgery and used RNA sequencing to describe an lncRNA profile. We then identified a list of lncRNAs that were differentially expressed between pairs of samples before and after the ischemic insult of cardiopulmonary bypass. The expression of some of these lncRNAs correlates with ischemic time. Coding genes in close proximity to differentially expressed lncRNAs and coding genes that have coordinated expression with these lncRNAs are enriched in functional categories related to myocardial infarction, including heart function, metabolism, the stress response, and the immune system.

Conclusions—

We describe a list of lncRNAs that are differentially expressed after ischemia in the human heart. These genes are predicted to function in pathways consistent with myocardial injury. As a result, lncRNAs may serve as novel diagnostic and therapeutic targets for ischemic heart disease.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00985049.
Inhibition of KLF5–Myo9b–RhoA Pathway–Mediated Podosome Formation in Macrophages Ameliorates Abdominal Aortic Aneurysm
Authors: Ma Dong , Zheng Bin , Suzuki Toru , Zhang Ruonan , Jiang Chunyang , Bai Disi , Yin Weina , Yang Zhan , Zhang Xinhua , Hou Lianguo , Zhan Hong , Wen Jin-kun
Published: January 2017

Rationale:

Abdominal aortic aneurysms (AAAs) are characterized by pathological remodeling of the aortic wall. Although both increased Krüppel-like factor 5 (KLF5) expression and macrophage infiltration have been implicated in vascular remodeling, the role of KLF5 in macrophage infiltration and AAA formation remains unclear.

Objective:

To determine the role of KLF5 in AAA formation and macrophage infiltration into AAAs.

Methods and Results:

KLF5 expression was significantly increased in human AAA tissues and in 2 mouse models of experimental AAA. Moreover, in myeloid-specific Klf5 knockout mice (myeKlf5
−/−
mice), macrophage infiltration, medial smooth muscle cell loss, elastin degradation, and AAA formation were markedly decreased. In cell migration and time-lapse imaging analyses, the migration of murine myeKlf5
−/−
macrophages was impaired, and in luciferase reporter assays, KLF5 activated Myo9b (myosin IXB) transcription by direct binding to the Myo9b promoter. In subsequent coimmunostaining studies, Myo9b was colocalized with filamentous actin, cortactin, vinculin, and Tks5 in the podosomes of phorbol 12,13-dibutyrate–treated macrophages, indicating that Myo9b participates in podosome formation. Gain- and loss-of-function experiments showed that KLF5 promoted podosome formation in macrophages by upregulating Myo9b expression. Furthermore, RhoA-GTP levels increased after KLF5 knockdown in macrophages, suggesting that KLF5 lies upstream of RhoA signaling. Finally, Myo9b expression was increased in human AAA tissues, located in macrophages, and positively correlated with AAA size.

Conclusions:

These data are the first to indicate that KLF5-dependent regulation of Myo9b/RhoA is required for podosome formation and macrophage migration during AAA formation, warranting consideration of the KLF5–Myo9b–RhoA pathway as a therapeutic target for AAA treatment.
Ablation of Interferon Regulatory Factor 3 Protects Against Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Liu Hui , Cheng Wen-Lin , Jiang Xi , Wang Pi-Xiao , Fang Chun , Zhu Xue-Yong , Huang Zan , She Zhi-Gang , Li Hongliang
Published: January 2017

The secretion of adhesion molecules by endothelial cells, as well as the subsequent infiltration of macrophages, determines the initiation and progression of atherosclerosis. Accumulating evidence suggests that IRF3 (interferon regulatory factor 3) is required for the induction of proinflammatory cytokines and for endothelial cell proliferation. However, the effect and underlying mechanism of IRF3 on atherogenesis remain unknown. Our results demonstrated a moderate-to-strong immunoreactivity effect associated with IRF3 in the endothelium and macrophages of the atherosclerotic plaques in patients with coronary heart disease and in hyperlipidemic mice. IRF3
−
/
−
ApoE
−/−
mice showed significantly decreased atherosclerotic lesions in the whole aorta, aortic sinus, and brachiocephalic arteries. The bone marrow transplantation further suggested that the amelioration of atherosclerosis might be attributed to the effects of IRF3 deficiency mainly in endothelial cells, as well as in macrophages. The enhanced stability of atherosclerotic plaques in IRF3
−/−
ApoE
−/−
mice was characterized by the reduction of necrotic core size, macrophage infiltration, and lipids, which was accompanied by increased collagen and smooth muscle cell content. Furthermore, multiple proinflammatory cytokines showed a marked decrease in IRF3
−/−
ApoE
−/−
mice. Mechanistically, IRF3 deficiency suppresses the secretion of VCAM-1 (vascular cell adhesion molecule 1) and the expression of ICAM-1 (intercellular adhesion molecule 1) by directly binding to the ICAM-1 promoter, which subsequently attenuates macrophage infiltration. Thus, our study suggests that IRF3 might be a potential target for the treatment of atherosclerosis development.
Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation
Authors: Gosse Philippe , Cremer Antoine , Pereira Helena , Bobrie Guillaume , Chatellier Gilles , Chamontin Bernard , Courand Pierre-Yves , Delsart Pascal , Denolle Thierry , Dourmap Caroline , Ferrari Emile , Girerd Xavier , Michel Halimi Jean , Herpin Daniel , Lantelme Pierre , Monge Matthieu , Mounier-Vehier Claire , Mourad Jean-Jacques , Ormezzano Olivier , Ribstein Jean , Rossignol Patrick , Sapoval Marc , Vaïsse Bernard , Zannad Faiez , Azizi Michel
Published: January 2017

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index (
P
=0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%;
P
=0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01570777.
Females Are Protected From Iron‐Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress
Authors: Das Subhash K. , Patel Vaibhav B. , Basu Ratnadeep , Wang Wang , DesAulniers Jessica , Kassiri Zamaneh , Oudit Gavin Y.
Published: January 2017

Background

Sex‐related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron‐overload cardiomyopathy is poorly understood.

Methods and Results

Male and female wild‐type and hemojuvelin‐null mice were injected and fed with a high‐iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron‐overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron‐overloaded mice based on echocardiographic and invasive pressure‐volume analyses. Female mice demonstrated a marked suppression of iron‐mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron‐overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron‐induced upregulation of ferritin, decreased myocardial
SERCA
2a levels, and increased
NCX
1 levels. 17β‐Estradiol therapy rescued the iron‐overload cardiomyopathy in male wild‐type mice. The responses in wild‐type and hemojuvelin‐null female mice were remarkably similar, highlighting a conserved mechanism of sex‐dependent protection from iron‐overload‐mediated cardiac injury.

Conclusions

Male and female mice respond differently to iron‐overload‐mediated effects on heart structure and function, and females are markedly protected from iron‐overload cardiomyopathy. Ovariectomy in female mice exacerbated iron‐induced myocardial injury and precipitated severe cardiac dysfunction during iron‐overload conditions, whereas 17β‐estradiol therapy was protective in male iron‐overloaded mice.
Colloquium Response
Authors: Kenny Paul
Published: January 2017

The problem for Study of Religions (sor) in the academy is the dearth of successful theory-as-explanation in the field and the consequential domination of the public square by other voices namely theology, apologetics, humanist study that privileges belief and New Atheism. There is theory-as-critique aplenty and it is applied to both religious truth claims and to explanatory theories about religion. Scholars ofsorhave the critical tools, methods, expertise and weight of scholarship to error check and to disprove naturalistic explanations but finding explanatory ground to stand on is very hard indeed. This piece argues that it is important to renew and revitalise the search for explanation.
Protecting the Malacca and Singapore Straits from Ships’ Atmospheric Emissions through the Implementation of marpol Annex vi
Authors: George Mary , Osman Abdul Samad Shaik , Hussin Hanafi , George Anneliz Reina
Published: January 2017

The International Maritime Organization (imo) adopted legally binding regulations for the control of ships’ atmospheric emissions under Annex vi of the International Convention for the Prevention of Marine Pollution from Ships, 1973/78. With Singapore, Malaysia and Indonesia being States Parties thereto, consequently, one of the effects in the Malacca and Singapore Straits is that it enables the Straits States, together with the imo, to designate emission control areas for the approximately 75,000 ships transiting annually. This article examines the robust provisions of Annex vi for the marine environmental protection of the Straits and the contentious debates preceding an otherwise dead-locked technology-transfer resolution for implementing Annex vi. If implemented, Annex vi provisions will represent a unique milestone in the protection of the marine environment of the Straits which is regulated by the restrictive provisions of Part iii of the 1982 United Nations Convention on the Law of the Sea.
The Israeli Supreme Court and Bedouin Land Claims in the Negev: A Missed Opportunity to Uphold Human and Indigenous Rights
Authors: Margalit Alon
Published: January 2017

This article critically discusses two judgments, recently delivered by the Israeli Supreme Court, which concern Bedouin land rights in the Negev (Al-Naqab), southern Israel. It is submitted that the narrow approach taken by the Court ignores the Bedouin traditional lifestyle and land tenure systems, thus preventing members of this indigenous and minority group from fully enjoying their human rights, and exposing them to further displacement and dispossession by Israeli authorities. The article also explains the relevance of these decisions to the Bedouin living in Area C of the West Bank which is occupied by Israel.
The Protection of Indigenous Peoples’ Lands by Domestic Legislation on Climate Change Response Measures: Exploring Potentials in the Regional Human Rights System of Africa
Authors: Jegede Ademola Oluborode
Published: January 2017

The need for protecting indigenous peoples’ lands as human rights in domestic legislation dealing with climate change response measures, that is, initiatives meant to address adverse effects of climate change, has been emphasised in a range of resolutions and decisions made under the auspices of the United Nations Human Rights Council (unhrc) and the United Nations Framework on Climate Change Convention (unfccc). Where domestic legislation on climate change response measures fails to protect adequately indigenous peoples’ lands, what potentials exist within the African human rights system? Using Nigeria, Zambia and Tanzania as illustration, this article demonstrates how key legislation dealing with climate change response measures fails to protect indigenous peoples’ lands in Africa. It then explores potentials within the African regional human rights system for addressing the inadequate gap existing within domestic legislation on the protection of indigenous peoples’ lands in the context of climate change response measures in Africa.
Atmospheric and Oceanic Origins of Tropical Precipitation Variability
Authors: He Jie , Deser Clara , Soden Brian J.
Published: January 2017

The intrinsic atmospheric and ocean-induced tropical precipitation variability is studied using millennial control simulations with various degrees of ocean coupling. A comparison between the coupled simulation and the atmosphere-only simulation with climatological sea surface temperatures (SSTs) shows that a substantial amount of tropical precipitation variability is generated without oceanic influence. This intrinsic atmospheric variability features a red noise spectrum from daily to monthly time scales and a white noise spectrum beyond the monthly time scale. The oceanic impact is inappreciable for submonthly time scales but important at interannual and longer time scales. For time scales longer than a year, it enhances precipitation variability throughout much of the tropical oceans and suppresses it in some subtropical areas, preferentially in the summer hemisphere. The sign of the ocean-induced precipitation variability can be inferred from the local precipitation–SST relationship, which largely reflects the local feedbacks between the two, although nonlocal forcing associated with El Niño–Southern Oscillation also plays a role. The thermodynamic and dynamic nature of the ocean-induced precipitation variability is studied by comparing the fully coupled and slab ocean simulations. For time scales longer than a year, equatorial precipitation variability is almost entirely driven by ocean circulation, except in the Atlantic Ocean. In the rest of the tropics, ocean-induced precipitation variability is dominated by mixed layer thermodynamics. Additional analyses indicate that both dynamic and thermodynamic oceanic processes are important for establishing the leading modes of large-scale tropical precipitation variability. On the other hand, ocean dynamics likely dampens tropical Pacific variability at multidecadal time scales and beyond.
Evaluation of Integrated Multisatellite Retrievals for GPM (IMERG) over Southern Canada against Ground Precipitation Observations: A Preliminary Assessment
Authors: Asong Z. E. , Razavi S. , Wheater H. S. , Wong J. S.
Published: January 2017

The Global Precipitation Measurement (GPM) mission offers new opportunities for modeling a range of physical/hydrological processes at higher resolutions, especially for remote river systems where the hydrometeorological monitoring network is sparse and weather radar is not readily available. In this study, the recently released Integrated Multisatellite Retrievals for GPM [version 03 (V03) IMERG Final Run] product with high spatiotemporal resolution of 0.1° and 30 min is evaluated against ground-based reference measurements (at the 6-hourly, daily, and monthly time scales) over different terrestrial ecozones of southern Canada within a 23-month period from 12 March 2014 to 31 January 2016. While IMERG and ground-based observations show similar regional variations of mean daily precipitation, IMERG tends to overestimate higher monthly precipitation amounts over the Pacific Maritime ecozone. Results from using continuous as well as categorical skill metrics reveal that IMERG shows more satisfactory agreement at the daily and the 6-hourly time scales for the months of June–September, unlike November–March. In terms of precipitation extremes (defined by the 75th percentile threshold for reference data), apart from a tendency toward overdetection of heavy precipitation events, IMERG captured well the distribution of heavy precipitation amounts and observed wet/dry spell length distributions over most ecozones. However, low skill was found over large portions of the Montane Cordillera ecozone and a few stations in the Prairie ecozone. This early study highlights a potential applicability of V03 IMERG Final Run as a reliable source of precipitation estimates in diverse water resources and hydrometeorological applications for different regions in southern Canada.