bluuebunny/crossref_metadata_2025 huggingface dataset:
On the set of expansive measures
Authors: Lee Keonhee , Morales C. A. , Shin Bomi
Published: October 2017

We prove that the set of expansive measures of a homeomorphism of a compact metric space is a [Formula: see text] subset of the space of Borel probability measures equipped with the weak* topology. Next that every expansive measure of a homeomorphism of a compact metric space can be weak* approximated by expansive measures with invariant support. In addition, if the expansive measures of a homeomorphism of a compact metric space are dense in the space of Borel probability measures, then there is an expansive measure whose support is both invariant and close to the whole space with respect to the Hausdorff metric. Henceforth, if the expansive measures are dense in the space of Borel probability measures, the set of heteroclinic points has no interior and the space has no isolated points.
Multidimensional knowledge-based framework is an essential step in the categorization of gene sets in complex disorders
Authors: Sreeja A. , Vinayan K. P.
Published: October 2017

In complex disorders, collaborative role of several genes accounts for the multitude of symptoms and the discovery of molecular mechanisms requires proper understanding of pertinent genes. Majority of the recent techniques utilize either single information or consolidate the independent outlook from multiple knowledge sources for assisting the discovery of candidate genes. In any case, given that various sorts of heterogeneous sources are possibly significant for quality gene prioritization, every source bearing data not conveyed by another, we assert that a perfect strategy ought to give approaches to observe among them in a genuine integrative style that catches the degree of each, instead of utilizing a straightforward mix of sources. We propose a flexible approach that empowers multi-source information reconciliation for quality gene prioritization that augments the complementary nature of various learning sources so as to utilize the maximum information of aggregated data. To illustrate the proposed approach, we took Autism Spectrum Disorder (ASD) as a case study and validated the framework on benchmark studies. We observed that the combined ranking based on integrated knowledge reduces the false positive observations and boosts the performance when compared with individual rankings. The clinical phenotype validation for ASD shows that there is a significant linkage between top positioned genes and endophenotypes of ASD. Categorization of genes based on endophenotype associations by this method will be useful for further hypothesis generation leading to clinical and translational analysis. This approach may also be useful in other complex neurological and psychiatric disorders with a strong genetic component.
On-Chip Break Junctions and Period-Adjustable Grating Driven by Thermal Stress
Authors: Wang Ling , Zhao Zhikai , Xiang Dong
Published: October 2017

The investigation of the electron transport through single molecule needs an efficient method to generate stable molecular junctions. There are various techniques, such as mechanically controllable break junction (MCBJ) technique and electromigration technique, to generate stable nanogaps and stable molecular junctions. However, it is a great challenge for MCBJ technique to obtain on-chip molecular junctions because of the constraint of the push rod components, which do not make it facile to fabricate highly integrated molecular devices. Meanwhile, the gap size between electrodes is nonadjustable for the electromigration method, which leads to a low yield of molecular junctions. In this report, a thermally controllable break junction method, which can overcome the above problem, is proposed for the first time. The device is based on a double-V-shaped symmetrical structure and mechanically driven by thermal expansion, thus the push rod is not needed. Furthermore, we proposed that the thermally controlled double-V-shaped structure can be employed to precisely adjust the period of the metal grating with nanometer accuracy, which is unavailable in other methods.
Performance Enhancement of a Refrigerator Using Phase Change Material-Based Condenser: An Experimental Investigation
Authors: Dandotiya Devendra , Banker N. D.
Published: October 2017

Tropical countries like India, the ambient temperature reaches to 45–50[Formula: see text]C in the summer and higher ambient temperature directly impacts the energy required by the household refrigerator. This paper presents an experimental performance of a domestic refrigerator incorporated with a phase change material (PCM)-based condenser in parallel to the conventional wire-and-tube air-cooled condenser for the climatic conditions of India. It is proposed to operate the refrigerator with the PCM-based condenser, while the ambient temperature is higher during the day, otherwise with the air-cooled condenser. Due to large latent heat storage capacity of the PCM, the condenser temperature would not increase significantly. The COP of the PCM-based condenser was 28% higher as compared to air cooled condenser for 60[Formula: see text]min which reduce to 3% as PCM temperature reached to 33[Formula: see text]C. The energy consumption is lower by [Formula: see text]% in [Formula: see text][Formula: see text]h of refrigerator experimentation with the proposed modification.
Reversible Jump Metropolis Light Transport Using Inverse Mappings
Authors: Bitterli Benedikt , Jakob Wenzel , Novák Jan , Jarosz Wojciech
Published: October 2017

We study Markov Chain Monte Carlo (MCMC) methods operating in primary sample space and their interactions with multiple sampling techniques. We observe that incorporating the sampling technique into the state of the Markov Chain, as done in Multiplexed Metropolis Light Transport, impedes the ability of the chain to properly explore the path space, as transitions between sampling techniques lead to disruptive alterations of path samples. To address this issue, we reformulate Multiplexed MLT in the Reversible Jump MCMC framework (RJMCMC) and introduce
inverse
sampling techniques that turn light paths into the random numbers that would produce them. This allows us to formulate a novel perturbation that can locally transition between sampling techniques without changing the geometry of the path, and we derive the correct acceptance probability using RJMCMC. We investigate how to generalize this concept to non-invertible sampling techniques commonly found in practice, and introduce
probabilistic
inverses that extend our perturbation to cover most sampling methods found in light transport simulations. Our theory reconciles the inverses with RJMCMC yielding an unbiased algorithm, which we call
Reversible Jump MLT
. We verify the correctness of our implementation in canonical and practical scenarios and demonstrate improved temporal coherence, decrease in structured artifacts, and faster convergence on a wide variety of scenes.
Response to: Comment on “Does the Equivalence between Gravitational Mass and Energy Survive for a Composite Quantum Body?”
Authors: Lebed A. G.
Published: October 2017

We have recently shown that both passive and active gravitational masses of a composite body are not equivalent to its energy due to some quantum effects. We have also suggested idealized and more realistic experiments to detect the above-mentioned inequivalence for a passive gravitational mass. The suggested idealized effect is as follows. A spacecraft moves protons of a macroscopic ensemble of hydrogen atoms with constant velocity in the Earth’s gravitational field. Due to nonhomogeneous squeezing of space by the field, electron ground state wave function experiences time-dependent perturbation in each hydrogen atom. This perturbation results in the appearance of a finite probability for an electron to be excited at higher energy levels and to emit a photon. The experimental task is to detect such photons from the ensemble of the atoms. More realistic variants of such experiment can be realized in solid crystals and nuclei, as first mentioned by us. In his recent comment on our paper, Crowell has argued that the effect, suggested by us, contradicts the existing experiments and, in particular, astronomic data. We show here that this conclusion is incorrect and based on the so-called “free fall” experiments, where our effect does not have to be observed.
Quality of Care of Patients with Diabetes in Primary Health Services in Southeast Brazil
Authors: Simão Christiane Chaves Augusto Leite , Costa Mônica Barros , Colugnati Fernando Antônio Basile , de Paula Elaine Amaral , Vanelli Chislene Pereira , de Paula Rogério Baumgratz
Published: October 2017

Background. Diabetes management involves multiple aspects that go beyond drug therapy as a way of providing high quality care. The objective of this study was to describe quality of care indicators for individuals with diabetes in southeast Brazil and to explore associations among these indicators. Methods. In this cross-sectional, observational study, health care providers filled out a questionnaire addressing health care structure and processes at 14 primary health care units (PHCUs). Clinical and laboratory data of diabetic patients attending the PHCUs and from patients referred to a secondary health care (SHC) center were collected. Results. There was a shortage of professionals in 53.8% of the PHCUs besides a high proportion of problems regarding referrals to SHC. At the PHCU, glycated hemoglobin results were available only in half of the medical records. A low rate of adequate glycemic control was also observed. An association between structure and process indicators and the outcomes analyzed was not found. Conclusion. Major deficiencies were found in the structure and processes of the PHCUs, in addition to unsatisfactory diabetes care outcomes. However, no association between structure, process, and outcomes was found.
Study on the Confidence and Reliability of the Mean Seismic Probability Risk Model
Authors: Wang Xiao-Lei , Lu Da-Gang
Published: October 2017

The mean seismic probability risk model has widely been used in seismic design and safety evaluation of critical infrastructures. In this paper, the confidence levels analysis and error equations derivation of the mean seismic probability risk model are conducted. It has been found that the confidence levels and error values of the mean seismic probability risk model are changed for different sites and that the confidence levels are low and the error values are large for most sites. Meanwhile, the confidence levels of ASCE/SEI 43-05 design parameters are analyzed and the error equation of achieved performance probabilities based on ASCE/SEI 43-05 is also obtained. It is found that the confidence levels for design results obtained using ASCE/SEI 43-05 criteria are not high, which are less than 95%, while the high confidence level of the uniform risk could not be achieved using ASCE/SEI 43-05 criteria and the error values between risk model with target confidence level and mean risk model using ASCE/SEI 43-05 criteria are large for some sites. It is suggested that the seismic risk model considering high confidence levels instead of the mean seismic probability risk model should be used in the future.
Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin
Authors: Carrasco-Torres Gabriela , Baltiérrez-Hoyos Rafael , Andrade-Jorge Erik , Villa-Treviño Saúl , Trujillo-Ferrara José Guadalupe , Vásquez-Garzón Verónica Rocío
Published: October 2017

The inflammatory condition of malignant tumors continually exposes cancer cells to reactive oxygen species, an oxidizing condition that leads to the activation of the antioxidant defense system. A similar activation occurs with glutathione production. This oxidant condition enables tumor cells to maintain the energy required for growth, proliferation, and evasion of cell death. The objective of the present study was to determine the effect on hepatocellular carcinoma cells of a combination treatment with maleic anhydride derivatives (prooxidants) and quercetin (an antioxidant). The results show that the combination of a prooxidant/antioxidant had a cytotoxic effect on HuH7 and HepG2 liver cancer cells, but not on either of two normal human epithelial cell lines or on primary hepatocytes. The combination treatment triggered apoptosis in hepatocellular carcinoma cells by activating the intrinsic pathway and causing S phase arrest during cell cycle progression. There is also clear evidence of a modification in cytoskeletal actin and nucleus morphology at 24 and 48 h posttreatment. Thus, the current data suggest that the combination of two anticarcinogenic drugs, a prooxidant followed by an antioxidant, can be further explored for antitumor potential as a new treatment strategy.
Inhibitory Effect of Propolis on Platelet Aggregation In Vitro
Authors: Zhang Yun-Xiang , Yang Ting-Ting , Xia Liu , Zhang Wei-Fen , Wang Jia-Fu , Wu Ya-Ping
Published: October 2017

Platelet hyperactivity plays an important role in arterial thrombosis and atherosclerosis. The present study was aimed to investigate the effects of different extracts of propolis and components of flavonoids on platelet aggregation. Platelet-rich plasma was prepared and incubated in vitro with different concentrations of the tested extracts and components of flavonoids. Platelets aggregation was induced by different agonists including adenosine diphosphate (ADP, 10 μM), thrombin receptor activator peptide (TRAP, 50 μM), and collagen (5 μg/mL). At 25 mg/L to 300 mg/mL, the water extract propolis (WEP) inhibited three agonists-induced platelet aggregations in a dose-dependent manner. The flavonoids isolated from the propolis also showed markedly inhibited platelet aggregation induced by collagen, ADP, and TRAP, respectively. The components including caffeic acid phenethyl ester (CAPE), galangin, apigenin, quercetin, kaempferol, ferulic acid, rutin, chrysin, pinostrobin, and pinocembrin and their abilities of inhibiting platelet aggregation were studied. It was concluded that propolis had an antiplatelet action in which flavonoids were mainly implicated.
Deep Hierarchical Representation from Classifying Logo-405
Authors: Hou Sujuan , Lin Jianwei , Zhou Shangbo , Qin Maoling , Jia Weikuan , Zheng Yuanjie
Published: October 2017

We introduce a logo classification mechanism which combines a series of deep representations obtained by fine-tuning convolutional neural network (CNN) architectures and traditional pattern recognition algorithms. In order to evaluate the proposed mechanism, we build a middle-scale logo dataset (named Logo-405) and treat it as a benchmark for logo related research. Our experiments are carried out on both the Logo-405 dataset and the publicly available FlickrLogos-32 dataset. The experimental results demonstrate that the proposed mechanism outperforms two popular ways used for logo classification, including the strategies that integrate hand-crafted features and traditional pattern recognition algorithms and the models which employ deep CNNs.
Diffusion Behaviors of Hydrogen Isotopes in Incoloy 800H: A First-Principles Study
Authors: Chen Hongyu , Li Hong , Li Chuan , Cao Jianzhu , Fang Chao
Published: October 2017

Incoloy 800H is one of the main stainless steel materials used in steam generators with High Temperature Reactor Pebble-bed Modules (HTR-PM). In this study, the diffusion behaviors of hydrogen isotopes in Incoloy 800H were investigated with first-principle calculations. Numerical results reveal that the starting and ending positions of the diffusion process are the two adjacent and most stable octahedral sites surrounded by Fe atoms and Ni atoms, and the diffusion follows an indirect path via the metastable tetrahedral sites and octahedral sites surrounded by Fe atoms and Cr atoms. The diffusion activation energies of hydrogen (H), deuterium (D), and tritium (T) in Incoloy 800H are investigated by first-principles calculations with the same approximate value of Q=0.757 eV; the diffusion coefficient frequency factors are also obtained with values of D0=1.56×10-6, 1.10×10-6, and 8.99×10-7 (m2/s) for H, D, and T, respectively. Furthermore, the theoretical results are compared with the experimental data, and it is found that both are in agreement with each other. These results are very helpful for understanding the diffusion behaviors of hydrogen isotopes in Incoloy 800H and can be used to guide the tritium source term analysis of secondary circuits in HTR-PM, which are first studied from a microperspective.
Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide‐Dependent Tolerance Pathway
Authors: Vriens Kim , Kumar Phalguni Tewari , Struyfs Caroline , Cools Tanne L. , Spincemaille Pieter , Kokalj Tadej , Sampaio-Marques Belém , Ludovico Paula , Lammertyn Jeroen , Cammue Bruno P. A. , Thevissen Karin
Published: October 2017

Amphotericin B (AmB) induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB‐induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB’s fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L‐NAME was used to interfere with nitric oxide radical production. L‐NAME increased and accelerated AmB‐induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S‐nitrosoglutathione inhibited AmB’s action. Hence, superoxide radicals were important for AmB’s fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L‐NAME, pointing to the potential of AmB‐L‐NAME combination therapy to treat fungal infections.
Preinoculation of Soybean Seeds Treated with Agrichemicals up to 30 Days before Sowing: Technological Innovation for Large-Scale Agriculture
Authors: Araujo Ricardo Silva , Cruz Sonia Purin da , Souchie Edson Luiz , Martin Thomas Newton , Nakatani André Shigueyoshi , Nogueira Marco Antonio , Hungria Mariangela
Published: October 2017

The cultivation of soybean in Brazil experienced an expressive growth in the last decades. Soybean is highly demanding on nitrogen (N) that must come from fertilizers or from biological fixation. The N supply to the soybean crop in Brazil relies on the inoculation with elite strains ofBradyrhizobium japonicum, B. elkanii,andB. diazoefficiens, which are able to fulfill the crop’s N requirements and enrich the soil for the following crop. The effectiveness of the association between N2-fixing bacteria and soybean plants depends on the efficacy of the inoculation process. Seed treatment with pesticides, especially fungicides or micronutrients, may rapidly kill the inoculated bacteria, affecting the establishment and outcome of the symbiosis. The development of technologies that allow inoculation to become a successful component of industrial seed treatment represents a valuable tool for the seed industry, as well as for the soybean crop worldwide. In this article, we report the results of new technologies, developed by the company Total Biotecnologia Indústria e Comércio S/A of Brazil, for preinoculation of soybean seeds with bradyrhizobia, in the presence of agrichemicals. Our results demonstrate improved bacterial survival for up to 30 days after inoculation, without compromising nodulation, N2-fixation, and yield in the field.
Report on 14 Large Whales That Died due to Ship Strikes off the Coast of Sri Lanka, 2010–2014
Authors: Nanayakkara Ranil P. , Herath H. M. J. C. B.
Published: October 2017

The greatest threat to cetaceans in Sri Lankan waters was considered to be the direct take of small- and medium-sized cetaceans using harpoons and/or as bycatch until recently. However, ship strikes have probably been occurring for years but have not been recognized for what they were. For the current study, only animals with visible and prominent injuries related to collisions were evaluated. Data gathered between 2010 and 2014 included the species, morphometry, location, and date; tissue samples were collected for genetic analysis. When possible, a complete necropsy was conducted; otherwise, partial necropsies were conducted. The study confirmed 14 reports of ship strikes between whales and vessels out of all the strandings reported from 2010 to 2014. Most strikes (n=09, 64%) involved blue whales (Balaenoptera musculus), although three other species were also documented, one Cuvier’s beaked whale, two great sperm whales, and one Bryde’s whale, as well as one unidentified baleen whale. Collision hotspots such as the southern waters of Sri Lanka are areas that warrant special attention in the form of vessel routing measures or speed limits, research on cetacean ecology, distribution, daily and seasonal movements, public service announcements, increased law enforcement presence, and other measures.
Analysis of the Relationship between Density and Mechanical Strength of Lightened Gypsums: Proposal for a Coefficient of Lightening
Authors: Santa Cruz Astorqui Jaime , del Río Merino Mercedes , Villoria Sáez Paola , Porras-Amores César
Published: October 2017

This article develops a relationship between the reduction of density in lightened gypsum and the addition of expanded and/or extruded polystyrene waste from the construction sector and their mechanical behavior. The equations determined in this study allow us to know the flexural and compressive strengths of a lightened gypsum/plaster compound once its density is known. The results show that there is an exponential relationship between the density of the compound and its strength. The methodology followed included a compilation of the results obtained in previous research works on lightweight gypsums, analyzing the relationship between density and mechanical strength and comparing them with the equations developed in this research. The results obtained by previous researchers have a good adjustment with the proposed models, and only perlite compounds present greater deviations in the compressive strength analysis. Also, a dimensionless lightening coefficient is defined which can help to determine the best application for a lightweight gypsum compound, comparing it with an ideal lightweight gypsum.
Prediction‐Based Control for Nonlinear Systems with Input Delay
Authors: Estrada-Sánchez I. , Velasco-Villa M. , Rodríguez-Cortés H.
Published: October 2017

This work has two primary objectives. First, it presents a state prediction strategy for a class of nonlinear Lipschitz systems subject to constant time delay in the input signal. As a result of a suitable change of variable, the state predictor asymptotically provides the value of the state τ units of time ahead. Second, it proposes a solution to the stabilization and trajectory tracking problems for the considered class of systems using predicted states. The predictor‐controller convergence is proved by considering a complete Lyapunov functional. The proposed predictor‐based controller strategy is evaluated using numerical simulations.
The PDZ-Binding Motif of HPV16-E6 Oncoprotein Modulates the Keratinization and Stemness Transcriptional ProfileIn Vivo
Authors: Cortés-Malagón Enoc Mariano , Palacios-Reyes Carmen , Romero-Cordoba Sandra , Mendoza-Villanueva Daniel , Escobar-Herrera Jaime , Verdejo-Torres Odette , Contreras Rubén Gerardo , Fernádez-Tilapa Gloria , Moreno-Eutimio Mario Adan , Moreno José , Hidalgo-Miranda Alfredo , Gariglio Patricio , Bonilla-Delgado José
Published: October 2017

Objective. The aim of this work was to compare the early gene expression profiles in the skin of HPV16-E6 transgenic mice regulated by the E6 PDZ-binding motif.Materials and Methods.The global transcriptional profiles in dorsal skin biopsies from K14E6 and K14E6Δ146-151 transgenic mice were compared using microarrays. Relevant genes obtained from the most differentially expressed processes were further examined by RT-qPCR, in situ RT-PCR, Western blot, or immunofluorescence.Results.The transcriptomic landscape of K14E6 versus K14E6Δ146-151 shows that the most affected expression profiles were those related to keratinocyte differentiation, stem cell maintenance, and keratinization. Additionally, downregulation of epidermal stemness markers such as K15 and CD34, as well as the upregulation of cytokeratin 6b, appeared to be dependent on the E6 PDZ-binding motif. Finally, wound healing, a physiological process linked to stemness, is impaired in the K14E6 mice compared to K14E6Δ146-151.Conclusion.The E6 PDZ-binding motif appears to affect stemness and keratinization during early stages of skin carcinogenesis. As E6 plays a significant role in HPV-induced skin carcinogenesis, the K14E6 versus K14E6Δ146-151 transcriptional profile provides a source of valuable data to uncover novel E6 functions in the skin.
Transmission Control of Electromagnetic Waves by Using Quarter-Wave Plate and Half-Wave Plate All-Dielectric Metasurfaces Based on Elliptic Dielectric Resonators
Authors: Yahyaoui Ali , Rmili Hatem , Achouri Karim , Sheikh Muntasir , Dobaie Abdullah , Affandi Adnan , Aguili Taoufik
Published: October 2017

We present the design of all-dielectric Quarter-Wave Plate (QWP) and Half-Wave Plate (HWP) metasurfaces based on elliptic dielectric resonators (EDRs) for the transmission control of electromagnetic waves over the frequency band 20–30 GHz. First, an extensive numerical analysis was realized by studying the effect of the resonators geometry (thickness and ellipticity) on the transmission of both x- and y-polarized waves. Then, based on the numerical analysis, we have realized and characterized experimentally both QWP and HWP all-dielectric metasurfaces.
Jejunal Diverticular Perforation Causing Small Bowel Obstruction in a Type 4 Hiatal Hernia: A Rare Case Report of a Nonagenarian Patient and Review of Relevant Literature
Authors: Biswas Saptarshi , Gogna Shekhar , Patel Prem
Published: October 2017

Type IV paraesophageal hernia (PEH) is very rare and is characterized by the intrathoracic herniation of the abdominal viscera other than the stomach into the chest. We describe a case of a 90-year-old male patient who presented at our emergency department complaining of epigastric pain that he had experienced over the past few hours and getting progressively worse. On the day after admission, his pain became severe. Chest radiography revealed an intrathoracic intestinal gas bubble; emergency exploratory laparotomy identified a type IV PEH with herniation of only the jejunum with perforated diverticula on mesenteric side through a hiatal defect into mediastinum. There are a few published cases of small bowel herniation into the thoracic cavity in the literature. Our patient represents a rare case of an individual diagnosed with type IV PEH with herniation of jejunum with perforated diverticula.
Analysis of Startup Process and Its Optimization for a Two-Stand Reversible Cold Rolling Mill
Authors: Liu Guangming , Li Yugui , Huang Qingxue , Yang Xia , Liu Aimin
Published: October 2017

Dynamic characteristic analysis of a two-stand reversible cold rolling mill in the startup process was carried out. The delay algorithm of the interstand thickness was proposed. A new method combined with the accelerated secant and the tangent methods was established to solve the simultaneous equations. The thickness and interstand tension transition processes with different static tension establishing processes were analyzed. Both mills were operated under constant rolling force control mode in the above process. The results show that the strip thickness in the rolling gap reduces in the static mill screwdown process. The entry stand runs inversely to establish the static interstand tension. This area becomes an abnormal thickness reduction area of the incoming strip. It results in several abnormal interstand tension increases in the subsequent startup process. The tension increase leads to an impact force on the strip that is the main reason of the strip breakage in the startup process. So the static tension establishing process was optimized, and the interstand tension fluctuation and the strip breakage accidents both reduced significantly. The results are beneficial to the startup process of the two-stand reversible cold rolling mill.
Evaluating the Use of Serum Inflammatory Markers for Preoperative Diagnosis of Infection in Patients with Nonunions
Authors: Wang Song , Yin Peng , Quan Chenliang , Khan Kamran , Wang Guoqi , Wang Lijuan , Cui Lin , Zhang Licheng , Zhang Lihai , Tang Peifu
Published: October 2017

Purpose. The aim of this study is to evaluate the effectiveness of laboratory serum tests in the diagnosis of infected nonunion.Methods. Forty-two patients suspected of having infected nonunion were investigated in the study. The serum levels of white blood-cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6) were measured. A positive diagnosis of infection was made on the basis of the positive culture results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each test were calculated.Results. The sensitivity and specificity of CRP both were higher than IL-6: 60.0% versus 57.1% and 85.7% versus 57.1%, respectively. With one, two, three, and four positive tests, the predicted probabilities of infection were 66.7%, 90.9%, 100%, and 100%, respectively, but the number of patients who had three or four positive tests was small.Conclusions. The diagnostic utility of IL-6 is inferior to CRP and the finding conflicts with previous conclusions drawn from periprosthetic infections. Laboratory analysis of serum inflammatory markers alone is not an effective screening tool for patients suspected of having an infected nonunion.
PACE4 Undergoes an Oncogenic Alternative Splicing Switch in Cancer
Authors: Couture Frédéric , Sabbagh Robert , Kwiatkowska Anna , Desjardins Roxane , Guay Simon-Pierre , Bouchard Luigi , Day Robert
Published: October 2017

Inhibition of PACE4, a proprotein convertase that is overexpressed in prostate cancer, has been shown to block cancer progression in an androgen-independent manner. However, the basis for its overexpression and its growth-inhibitory effects are mitigated and uncertain. Here, we report that PACE4 pre-mRNA undergoes DNA methylation–sensitive alternative splicing of its terminal exon 3′ untranslated region, generating an oncogenic, C-terminally modified isoform (PACE4-altCT). We found this isoform to be strongly expressed in prostate cancer cells, where it displayed an enhanced autoactivating process and a distinct intracellular routing that prevented its extracellular secretion. Together, these events led to a dramatic increase in processing of the progrowth differentiation factor pro-GDF15 as the first PACE4 substrate to be identified in prostate cancer. We detected robust expression of PACE4-altCT in other cancer types, suggesting that an oncogenic switch for this proenzyme may offer a therapeutic target not only in advanced prostate cancer but perhaps also more broadly in human cancer. Cancer Res; 77(24); 6863–79. ©2017 AACR.
Moonshot Acceleration Factor: Medical Imaging
Authors: Sevick-Muraca Eva M. , Frank Richard A. , Giger Maryellen L. , Mulshine James L.
Published: October 2017

Medical imaging is essential to screening, early diagnosis, and monitoring responses to cancer treatments and, when used with other diagnostics, provides guidance for clinicians in choosing the most effective patient management plan that maximizes survivorship and quality of life. At a gathering of agency officials, patient advocacy organizations, industry/professional stakeholder groups, and clinical/basic science academicians, recommendations were made on why and how one should build a “cancer knowledge network” that includes imaging. Steps to accelerate the translation and clinical adoption of cancer discoveries to meet the goals of the Cancer Moonshot include harnessing computational power and architectures, developing data sharing policies, and standardizing medical imaging and in vitro diagnostics. Cancer Res; 77(21); 5717–20. ©2017 AACR.
Sleeping Beauty Insertional Mutagenesis in Mice Identifies Drivers of Steatosis-Associated Hepatic Tumors
Authors: Tschida Barbara R. , Temiz Nuri A. , Kuka Timothy P. , Lee Lindsey A. , Riordan Jesse D. , Tierrablanca Carlos A. , Hullsiek Robert , Wagner Sandra , Hudson Wendy A. , Linden Michael A. , Amin Khalid , Beckmann Pauline J. , Heuer Rachel A. , Sarver Aaron L. , Yang Ju Dong , Roberts Lewis R. , Nadeau Joseph H. , Dupuy Adam J. , Keng Vincent W. , Largaespada David A.
Published: October 2017

Hepatic steatosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet little is known about the molecular pathology associated with this factor. In this study, we performed a forward genetic screen using Sleeping Beauty (SB) transposon insertional mutagenesis in mice treated to induce hepatic steatosis and compared the results to human HCC data. In humans, we determined that steatosis increased the proportion of female HCC patients, a pattern also reflected in mice. Our genetic screen identified 203 candidate steatosis-associated HCC genes, many of which are altered in human HCC and are members of established HCC-driving signaling pathways. The protein kinase A/cyclic AMP signaling pathway was altered frequently in mouse and human steatosis-associated HCC. We found that activated PKA expression drove steatosis-specific liver tumorigenesis in a mouse model. Another candidate HCC driver, the N-acetyltransferase NAT10, which we found to be overexpressed in human steatosis–associated HCC and associated with decreased survival in human HCC, also drove liver tumorigenesis in a steatotic mouse model. This study identifies genes and pathways promoting HCC that may represent novel targets for prevention and treatment in the context of hepatic steatosis, an area of rapidly growing clinical significance. Cancer Res; 77(23); 6576–88. ©2017 AACR.
A Large-Scale RNAi Screen Identifies SGK1 as a Key Survival Kinase for GBM Stem Cells
Authors: Kulkarni Shreya , Goel-Bhattacharya Surbhi , Sengupta Sejuti , Cochran Brent H.
Published: October 2017

Glioblastoma multiforme (GBM) is the most common type of primary malignant brain cancer and has a very poor prognosis. A subpopulation of cells known as GBM stem-like cells (GBM-SC) have the capacity to initiate and sustain tumor growth and possess molecular characteristics similar to the parental tumor. GBM-SCs are known to be enriched in hypoxic niches and may contribute to therapeutic resistance. Therefore, to identify genetic determinants important for the proliferation and survival of GBM stem cells, an unbiased pooled shRNA screen of 10,000 genes was conducted under normoxic as well as hypoxic conditions. A number of essential genes were identified that are required for GBM-SC growth, under either or both oxygen conditions, in two different GBM-SC lines. Interestingly, only about a third of the essential genes were common to both cell lines. The oxygen environment significantly impacts the cellular genetic dependencies as 30% of the genes required under hypoxia were not required under normoxic conditions. In addition to identifying essential genes already implicated in GBM such as CDK4, KIF11, and RAN, the screen also identified new genes that have not been previously implicated in GBM stem cell biology. The importance of the serum and glucocorticoid-regulated kinase 1 (SGK1) for cellular survival was validated in multiple patient-derived GBM stem cell lines using shRNA, CRISPR, and pharmacologic inhibitors. However, SGK1 depletion and inhibition has little effect on traditional serum grown glioma lines and on differentiated GBM-SCs indicating its specific importance in GBM stem cell survival.

Implications: This study identifies genes required for the growth and survival of GBM stem cells under both normoxic and hypoxic conditions and finds SGK1 as a novel potential drug target for GBM. Mol Cancer Res; 16(1); 103–14. ©2017 AACR.
Cell Cycle–Dependent Tumor Engraftment and Migration Are Enabled by Aurora-A
Authors: Chu Tony L.H. , Connell Marisa , Zhou Lixin , He Zhengcheng , Won Jennifer , Chen Helen , Rahavi Seyed M.R. , Mohan Pooja , Nemirovsky Oksana , Fotovati Abbas , Pujana Miguel Angel , Reid Gregor S.D. , Nielsen Torsten O. , Pante Nelly , Maxwell Christopher A.
Published: October 2017

Cell-cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells that are perceived as independent processes but may be interconnected by molecular pathways that control microtubule nucleation at centrosomes. Here, cell-cycle progression dramatically impacts the engraftment kinetics of 4T1-luciferase2 breast cancer cells in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multiparameter imaging of wound closure assays was used to track cell-cycle progression, cell migration, and associated phenotypes in epithelial cells or carcinoma cells expressing a fluorescence ubiquitin cell-cycle indicator. Cell migration occurred with an elevated velocity and directionality during the S–G2-phase of the cell cycle, and cells in this phase possess front-polarized centrosomes with augmented microtubule nucleation capacity. Inhibition of Aurora kinase-A (AURKA/Aurora-A) dampens these phenotypes without altering cell-cycle progression. During G2-phase, the level of phosphorylated Aurora-A at centrosomes is reduced in hyaluronan-mediated motility receptor (HMMR)-silenced cells as is the nuclear transport of TPX2, an Aurora-A–activating protein. TPX2 nuclear transport depends upon HMMR-T703, which releases TPX2 from a complex with importin-α (KPNA2) at the nuclear envelope. Finally, the abundance of phosphorylated HMMR-T703, a substrate for Aurora-A, predicts breast cancer–specific survival and relapse-free survival in patients with estrogen receptor (ER)–negative (n = 941), triple-negative (TNBC) phenotype (n = 538), or basal-like subtype (n = 293) breast cancers, but not in those patients with ER-positive breast cancer (n = 2,218). Together, these data demonstrate an Aurora-A/TPX2/HMMR molecular axis that intersects cell-cycle progression and cell migration.

Implications: Tumor cell engraftment, migration, and cell-cycle progression share common regulation of the microtubule cytoskeleton through the Aurora-A/TPX2/HMMR axis, which has the potential to influence the survival of patients with ER-negative breast tumors. Mol Cancer Res; 16(1); 16–31. ©2017 AACR.
Economic Evaluation of Intensive Inpatient Treatments for Severely Obese Children and Adolescents
Authors: Makkes Sabine , van Dongen Johanna M. , Renders Carry M. , van der Baan-Slootweg Olga H. , Seidell Jacob C. , Bosmans Judith E.
Published: October 2017

Background: Considering the large economic consequences of severe childhood obesity for the society, we aimed to conduct an economic evaluation comparing two intensive 1-year lifestyle treatments with varying inpatient periods for severely obese children and adolescents with regard to standard deviation score BMI (SDS-BMI) and quality-adjusted life years (QALYs). Methods: An economic evaluation from a societal perspective accompanying a randomized controlled trial with a 24-month follow-up. 80 participants (8-19 years) with severe obesity were included. Participants received an intensive 1-year lifestyle treatment with an inpatient period of 2 months (short-stay group) or 6 months (long-stay group). Data were collected at baseline, 6, 12 ,and 24 months and included SDS-BMI and QALYs. Results: SDS-BMI decreased in the first 6 months of treatment, stabilized in the second 6 months, and increased during the 2nd year in both groups. After 24 months, SDS-BMI was similar in both groups, but remained lower than baseline values (mean difference -0.24, 95% CI -0.42; -0.06). There was no difference in QALYs between the groups after 24 months. For SDS-BMI, the probability of the short-stay treatment being cost-effective in comparison with the long-stay treatment was 1 at a willingness-to-pay of 0 EUR/unit of effect, which slowly decreased to 0.54 for larger willingness-to-pay values. Conclusions: Based on the results of this study, the short-stay treatment is considered to be more cost-effective from the societal perspective in comparison with the long-stay treatment. Future research should provide insight in whether the short-stay treatment is cost-effective in comparison with usual care.
Principles of Current Vertebrate Neuromorphology
Authors: Nieuwenhuys Rudolf , Nieuwenhuys R.
Published: October 2017

Causal analysis of molecular patterning at neural plate and early neural tube stages has shown that the central nervous system (CNS) of vertebrates is essentially organized into transverse neural segments or neuromeres and longitudinal zones which follow the curved axis of the brain. The intersection of the longitudinal and transverse patterning processes in the embryonic brain leads to the formation of a checkerboard pattern of distinct progenitor domains called “fundamental morphological units” (FMUs). The topologically invariant pattern formed by the ventricular surfaces of the FMUs of a given taxon represents the “Bauplan” or “blueprint” of the brain of that taxon. The FMUs initially represent thin epithelial fields; during further development they are transformed into three-dimensional radial units, extending from the ventricular surface to the meningeal surface. It is of note that the boundaries of the neuromeres, longitudinal zones, and radial units all strictly adhere to a non-Cartesian coordinate system inherent to the CNS of all vertebrates. The major neural histogenetic processes, including cellular proliferation, radial migration, and differentiation, as well as the formation of grisea (cell masses, nuclei, and cortices), occur principally within the confines of the FMUs, although tangential migration may also take cells to distant sites. Hence, recognition and delimitation of these units is essential for the identification and interpretation of grisea. An outline of the procedure to be followed in these processes of identification and interpretation is presented, and a list of the pertinent homology criteria is provided.
Impact of Lipid-Inflammatory-Oxidative Metabolism on Auditory Skills after Hearing Aid Fitting in the Elderly
Authors: Lessa Alexandre Hundertmarck , Cruz Ivana Beatrice Mânica da , Manica-Cattani Maria Fernanda , Moresco Rafael Noal , Duarte Marta Maria Medeiros Frescura , Costa Maristela Julio
Published: October 2017

This study aimed to assess whether lipid-inflammatory-oxidative metabolism influences auditory processing skills, and whether they function in changing auditory performance after hearing aid fitting in the elderly. Twelve subjects with bilateral hearing loss were submitted to blood tests (to check their lipid-inflammatory-oxidative metabolism) and auditory processing skill tests. After 3 months of using the hearing aids, their auditory skills were re-evaluated and the data were correlated statistically. Oxidative stress levels mainly showed some impact on auditory temporal processing; such a relation and others should best be examined in further studies with larger populations.
Cerebrospinal Fluid Phosphate in Delirium after Hip Fracture
Authors: Idland Ane-Victoria , Wyller Torgeir Bruun , Støen Randi , Dahl Gry Torsæter , Frihagen Frede , Brækhus Anne , Hassel Bjørnar , Watne Leiv Otto
Published: October 2017

Aims: Phosphate is essential for neuronal activity. We aimed to investigate whether delirium is associated with altered phosphate concentrations in cerebrospinal fluid (CSF) and serum. Methods: Seventy-seven patients with hip fracture were assessed for delirium before and after acute surgery. Prefracture dementia was diagnosed by an expert panel. Phosphate was measured in CSF obtained immediately before spinal anesthesia (n = 77) and in serum (n = 47). CSF from 23 cognitively healthy elderly patients undergoing spinal anesthesia was also analyzed. Results: Hip fracture patients with prevalent delirium had higher CSF phosphate concentrations than those without delirium (median 0.63 vs. 0.55 mmol/L, p = 0.001). In analyses stratified on dementia status, this difference was only significant in patients with dementia. Serum phosphate was ∼1 mmol/L; there was no association between serum phosphate concentration and delirium status. CSF phosphate did not correlate with serum levels. Conclusion: Patients with delirium superimposed on dementia have elevated phosphate levels.
Dynamics of Goldfish Subregional Hippocampal Pallium Activity throughout Spatial Memory Formation
Authors: Ocaña Francisco M. , Uceda Sara , Arias Jorge L. , Salas Cosme , Rodríguez Fernando
Published: October 2017

The teleost fish hippocampal pallium, like the hippocampus of tetrapods, is essential for relational map-like spatial memories. In mammals, these relational memories involve the dynamic interactions among different hippocampal subregions and between the hippocampus-neocortex network, which performs specialized operations such as memory encoding and retrieval. However, how the teleost hippocampal homologue operates to achieve comparably sophisticated spatial cognition capabilities is largely unknown. In the present study, the progressive changes in the metabolic activity of the pallial regions that have been proposed as possible homologues of the mammalian hippocampus were monitored in goldfish. Quantitative cytochrome oxidase histochemistry was used to measure the level of activation along the rostrocaudal axis of the ventral (Dlv) and dorsal parts of the dorsolateral division (Dld) and in the dorsoposterior division (Dp) of the goldfish telencephalic pallium throughout the time course of the learning process of a spatial memory task. The results revealed a significant increase in spatial memory-related metabolic activity in the Dlv, but not in the Dld, suggesting that the Dlv, but not the Dld, is comparable to the amniote hippocampus. Regarding the Dlv, the level of activation of the precommissural Dlv significantly increased at training onset but progressively declined to finally return to the basal pretraining level when the animals mastered the spatial task. In contrast, the commissural Dlv activation persisted even when the acquisition phase was completed and the animal's performance reached an asymptotic level. These results suggest that, like the dentate gyrus of mammals, the goldfish precommissural Dlv seems to respond nonlinearly to increments of change in sensory input, performing pattern separation under highly dissimilar input patterns. In addition, like the CA3 of mammals, the commissural Dlv likely operates in a continuum between two modes, a pattern separation or storage operation mode at early acquisition when the change in the sensory input is high, probably driven by the precommissural Dlv output, and a pattern completion or recall operation mode when the animals have mastered the task and the change in sensory input is small. Finally, an unexpected result of the present study is the persistent activation of the area Dp throughout the complete spatial task training period, which suggests that the Dp could be an important component of the pallial network involved in spatial memory in goldfish, and supports the hypothesis proposing that the Dp is a specialized part of the hippocampal pallium network.