bluuebunny/crossref_metadata_2025 huggingface dataset:
IRF5 regulates unique subset of genes in dendritic cells during West Nile virus infection
Authors: Chow Kwan T , Driscoll Connor , Loo Yueh-Ming , Knoll Megan , Gale Michael
Published: November 2018

Pathogen recognition receptor (PRR) signaling is critical for triggering innate immune activation and the expression of immune response genes, including genes that impart restriction against virus replication. RIG-I-like receptors and TLRs are PRRs that signal immune activation and drive the expression of antiviral genes and the production of type I IFN leading to induction of IFN-stimulated genes, in part through the interferon regulatory factor (IRF) family of transcription factors. Previous studies with West Nile virus (WNV) showed that IRF3 and IRF7 regulate IFN expression in fibroblasts and neurons, whereas macrophages and dendritic cells (DCs) retained the ability to induce IFN-β in the absence of IRF3 and IRF7 in a manner implicating IRF5 in PRR signaling actions. Here we assessed the contribution of IRF5 to immune gene induction in response to WNV infection in DCs. We examined IRF5-dependent gene expression and found that loss of IRF5 in mice resulted in modest and subtle changes in the expression of WNV-regulated genes. Anti-IRF5 chromatin immunoprecipitation with next-generation sequencing of genomic DNA coupled with mRNA analysis revealed unique IRF5 binding motifs within the mouse genome that are distinct from the canonical IRF binding motif and that link with IRF5-target gene expression. Using integrative bioinformatics analyses, we identified new IRF5 primary target genes in DCs in response to virus infection. This study provides novel insights into the distinct and unique innate immune and immune gene regulatory program directed by IRF5.

IRF5 regulates distinct gene regulation programs associated with diverse cellular pathways following West Nile Virus infection in mouse dendritic cells.
Novel approach using transoral robotic surgery for resection of cervical spine chordoma
Authors: McCann Adam C. , Berger Connor , Mahmoud Ahmad F. , Kuan Edward C. , Malhotra Neil R. , O'Malley Bert W.
Published: November 2018

Chordomas are rare, infiltrative neoplasms of notochordal origin that present along the spinal canal; en bloc surgical resection is paramount to successful treatment. Limited visualization and complex anatomy are major challenges to resection of upper cervical spine chordomas and often require invasive surgery. A 27‐year‐old male presented with an incidentally discovered chordoma of the midline second cervical vertebra of the spine. To obtain en bloc resection of the lesion while both overcoming limitations due to access and without introducing morbidity from traditional anterior approaches, we elected using transoral robotic surgery for resection. Due to complete resection, the patient remains disease‐free and was spared adjuvant radiation. Laryngoscope, 129:1395–1399, 2019
Progression of hearing loss in neurofibromatosis type 2 according to genetic severity
Authors: Emmanouil Beatrice , Houston Rory , May Anne , Ramsden James D. , Hanemann C. Oliver , Halliday Dorothy , Parry Allyson , Mackeith Samuel
Published: November 2018

Objectives/Hypothesis

This study set out to describe the progression of hearing loss in patients with neurofibromatosis type 2 (NF2), treated in a quaternary multidisciplinary clinic. It also aimed to compare hearing loss across patients grouped according to a known genetic severity score to explore its utility for prognostication.

Study Design

Retrospective cohort study.

Methods

We conducted a study of 147 patients with confirmed NF2 diagnosis for a mean observational period of 10 years. Pure‐tone average (PTA), optimum discriminations scores (ODS), and genotype data were collected. Patients were classified according to hearing class (American Academy of Otolaryngology), their candidacy for auditory implantation (UK National NF2 consensus) and grouped by genetic severity as: 1 = tissue mosaic, 2A = mild classic, 2B = moderate classic, and 3 = severe. Survival analysis investigated the effect of genetic severity on the age of loss of serviceable hearing.

Results

Genetic severity was a significant predictor of hearing outcomes such as ODS, hearing classification, and maximum annual PTA deterioration. Although the overall median age of loss of serviceable hearing was 78 years, there was significant variation according to the genetic severity; the median for severe patients was 32 years compared to a median of 80 for tissue mosaic patients.

Conclusions

This is the first description of long‐term hearing outcomes in a clinical setting across a large heterogeneous cohort of patients with NF2. The results highlight the potential importance and benefit of considering the genetic severity score of patients when undertaking treatment decisions, as well as planning future natural history studies.

Level of Evidence

2c Laryngoscope, 129:974–980, 2019
Short refutations for an equivalence‐chain principle for constant‐depth formulas
Authors: Buss Sam , Ramyaa Ramyaa
Published: November 2018

We consider tautologies expressing equivalence‐chain properties in the spirit of Thapen and Krajíček, which are candidates for exponentially separating depth k and depth Frege proof systems. We formulate a special case where the initial member of the equivalence chain is fully specified and the equivalence‐chain implications are actually equivalences. This special case is shown to lead to polynomial size resolution refutations. Thus it cannot be used for separating depth k and depth propositional systems. We state some Håstad switching lemma conditions that restrict the possible propositional proofs in more general situations.
Polymacrocycles Derived via Ugi Multi‐Component Reactions
Authors: Dannecker Patrick‐Kurt , Sehlinger Ansgar , Meier Michael A. R.
Published: November 2018

The synthesis of macrocycles based on the Ugi‐4CR has been thoroughly explored by Wessjohann and coworkers, while polymerizations utilizing the Ugi‐4CR are already patented by Ugi and recently studied more in detail, developing a new trend in polymer chemistry. Here, the combination of both, that is, the synthesis of polymacrocycles, is demonstrated. As diverse functional groups can be easily introduced in a macrocycle via Ugi‐4CR, a straightforward design of polymacrocycles is achieved in a two‐step procedure. First, the Ugi‐4CR of 10‐undecenoic acid, a diamine, a diisocyanide, and an aldehyde results in diversely substituted macrocycles having two terminal double bonds. Subsequently, these macrocycles are polymerized by ADMET (acyclic diene metathesis) or thiol‐ene polymerization to generate polymacrocycles with potential application in coordination chemistry as, for example, sensors, filters, or phase‐transfer catalysts. Moreover, the setup of the literature‐known Ugi macrocyclization is simplified by systematic reaction screening.
Modeling piecewise planar fault discontinuities without element‐partitioning in 3D reservoir‐geomechanical models
Authors: Liu Chuanqi , Prévost Jean H. , Sukumar N.
Published: November 2018

Using the extended finite element method, faults can be introduced into a three‐dimensional reservoir‐geomechanical model without meshing to assess the potential for fault reactivation associated with industrial activities such as disposal of CO2 or fluid extraction. The residuals to the governing equations include basis functions formed from the enrichment functions for strong and weak discontinuities. The traditional spatial integration scheme is based on an algorithm that partitions each enriched element into a collection of subtetrahedra, which is time and storage intensive. To avoid element partitioning, we adopt the homogeneous numerical integration scheme (referred as HNI hereafter) where the integration of homogeneous monomials over each polyhedron is converted into the integration of the same monomials over the one‐dimensional edges of the polyhedron by using Stokes's theorem and Euler's homogeneous function theorem. The integrands for the strong and weak discontinuities are derived to implement the integration scheme in the three‐dimensional reservoir‐geomechanical model. An example of a jagged fault is presented to reveal the advantages of HNI scheme over the standard element partitioning approach. Several other examples that involve fluid flow, fault sliding, and fault sliding triggered by injection pressure are also presented to demonstrate that accurate and efficient computations are realized by the new integration scheme.
Biodegradable polymer/clay systems for highly controlled release of NPK fertilizer
Authors: Daitx Tales S. , Giovanela Marcelo , Carli Larissa N. , Mauler Raquel S.
Published: November 2018

The aim of this work was to obtain biodegradable polymeric systems based on poly(hydroxybutyrate) (PHB) for use in the controlled release of agrochemicals and to analyze the relationship between the properties of polymers and the rates of release of active compounds. Two types of systems were obtained: one using nitrogen, phosphorous, and potassium (NPK) fertilizer directly mixed within the polymer matrix and another with the fertilizer previously incorporated in bentonite (Bent) and mixed with the polymer. The systems were obtained by melt processing and then evaluated by their properties. The release of the active compounds was analyzed by conductometric analysis using an aqueous solution as release medium for 240 hours. The obtained results were correlated with the biodegradation process of PHB. All of the systems presented a significant reduction in the active compounds released to the environment as compared with the direct application of NPK. The PHB/NPK systems showed a release of up to 37% of the compounds, while the PHB/m‐Bent showed greater control, with a release between 4% and 11% after 240 hours. In addition, the properties of the polymer systems presented a direct relationship with the rate of active compounds released. The type of production process, properties, and biodegradability indicate interesting potential of these systems for application in the controlled release of active compounds.
Extremum seeking by a dynamic plant using mixed integral sliding mode controller with synchronous detection gradient estimation
Authors: Solis Cesar U. , Clempner Julio B. , Poznyak Alexander S.
Published: November 2018

This paper presents a continuous‐time optimization method for an unknown convex function restricted to a dynamic plant with an available output including a stochastic noise. For solving the problem, we propose an extremum seeking algorithm based on a modified synchronous detection method for computing a stochastic gradient descent approach. In order to reject from the beginning the undesirable uncertainties and perturbations of the dynamic plant, we employ the standard deterministic integral sliding mode control transforming the initial dynamic plant to the static one, and after (in fact, from the beginning of the process), we apply the gradient decedent technique. We consider time‐decreasing parameters for compensating the stochastic dynamics. We prove the stability and the mean‐square convergence of the method. To validate the exposition, we perform a numerical example simulation.
Lipidomics as a diagnostic tool of the metabolic and physiological state of managed whales: A correlation study of systemic metabolism
Authors: Tang Chuan‐Ho , Lin Ching‐Yu , Tsai Yi‐Lun , Lee Shu‐Hui , Wang Wei‐Hsien
Published: November 2018

Integrating multifactor blood analysis is a key step toward a precise diagnosis of the health status of marine mammals. Variations in the circulating lipid profile reflect changes in the metabolism and physiology of an individual. To demonstrate the practicability of lipid profiling for physiological assessment, the phosphorylcholine‐containing lipids in the plasma of long‐term managed beluga whales (Delphinapterus leucas) were profiled using a lipidomics methodology. Using a multivariate analysis, the mean corpuscular volume, cholesterol, potassium, and γ‐glutamyltranspeptidase levels were well modeled with the lipid profile of the female whales. In the models, the correlated lipids provided information about blood parameter‐related metabolism and physiological regulation, in particular relating to cholesterol and inflammation. In the males, the levels of cholesterol, triglycerides, blood urea nitrogen, creatinine, plasma iron, and segmented neutrophil were well modeled with the lipid profile. In addition to providing information about the related metabolism and regulation, through a cross‐linked analysis of the blood parameters, the correlated lipids indicated a parallel regulation involved in the energy metabolism of the male whales. Lipidomics as a method for revealing the context of physiological change shows practical potential for the health care of managed whales.
Conclusion
Authors: Lindsay Claire
Published: November 2018

By way of conclusion to the preceding arguments, this chapter, drawing on ideas from the new formalism and media studies history, pursues the implications of the magazines’ rhythm and serialization with respect to theories of nation-building in the context of post-revolutionary Mexico. In its summation of the ramifications of the book’s findings, it also returns to the suggestive idea of archive, first rehearsed in Chapter 1, to consider the concept’s material and epistemological value for this particular object of study.
Multi-centered higher spin solutions from $$ {\mathcal{W}}_N $$ conformal blocks
Authors: Hulík Ondřej , Raeymaekers Joris , Vasilakis Orestis
Published: November 2018

Abstract

Motivated by the question of bulk localization in holography, we study the problem of constructing multi-centered solutions in higher spin gravity which describe point particles in the interior of AdS3. In the Chern-Simons formulation these take into account the backreaction after adding Wilson line sources. We focus on chiral solutions where only the left-moving sector is excited. In that case it is possible to choose a gauge where the dynamical variables are a set of Toda fields living in the bulk. The problem then reduces to solving the

$$ {{\mathcal{A}}_N}_{-1} $$

A
N

−
1

Toda equations with delta function sources, which in turn requires solving an associated monodromy problem. We show that this monodromy problem is equivalent to the monodromy problem for a particular

$$ {\mathcal{W}}_N $$

W
N

vacuum conformal block at large central charge. Therefore, knowledge of the

$$ {\mathcal{W}}_N $$

W
N

vacuum block determines the multi-centered solution. Our calculations go beyond the heavy-light approximation by including the backreaction of all higher spin particles.
A Review of Physical and Numerical Approaches for the Study of Gas Stirring in Ladle Metallurgy
Authors: Liu Yu , Ersson Mikael , Liu Heping , Jönsson Pär Göran , Gan Yong
Published: November 2018

This article presents a review of the research into gas stirring in ladle metallurgy carried out over the past few decades. Herein, the physical modeling experiments are divided into four major areas: (1) mixing and homogenization in the ladle; (2) gas bubble formation, transformation, and interactions in the plume zone; (3) inclusion behavior at the steel–slag interface and in the molten steel; and (4) open eye formation. Several industrial trials have also been carried out to optimize gas stirring and open eye formation. Approaches for selecting criteria for scaling to guarantee flow similarity between industrial trials and physical modeling experiments are discussed. To describe the bubble behavior and two-phase plume structure, four main mathematical models have been used in different research fields: (1) the quasi-single-phase model, (2) the volume of fluid (VOF) model, (3) the Eulerian multiphase (E–E) model, and (4) the Eulerian–Lagrangian (E–L) model. In recent years, the E–E model has been used to predict gas stirring conditions in the ladle, and specific models in commercial packages, as well as research codes, have been developed gradually to describe the complex physical and chemical phenomena. Furthermore, the coupling of turbulence models with multiphase models is also discussed. For physical modeling, some general empirical rules have not been analyzed sufficiently. Based on a comparison with the available experimental results, it is found that the mathematical models focusing on the mass transfer phenomenon and inclusion behaviors at the steel-slag interface, vacuum degassing at the gas–liquid interface, dissolution rate of the solid alloy at the liquid–solid interface, and the combination of fluid dynamics and thermodynamics need to be improved further. To describe industrial conditions using mathematical methods and improve numerical modeling, the results of physical modeling experiments and industrial trials must offer satisfactory validations for the improvement of numerical modeling.
Evaluation of a single-cell protein as a dietary fish meal substitute for whiteleg shrimp Litopenaeus vannamei
Authors: Hamidoghli Ali , Yun Hyeonho , Won Seonghun , Kim SuKyung , Farris Nathaniel W. , Bai Sungchul C.
Published: November 2018

A 9-week feeding trial was conducted to evaluate the optimum dietary level of PROTIDE (PRO), a single-cell protein obtained from the bacteria Corynebacterium ammoniagenes, as a substitute for fish meal in the diet of whiteleg shrimp Litopenaeus vannamei. Five diets were formulated that replaced fish meal at 0% (PRO0), 10% (PRO2), 20% (PRO4), 30% (PRO6) and 40% (PRO8). Fifty shrimp averaging 0.15 ± 0.02 g (mean ± SD) body weight were randomly distributed between 20 experimental tanks and fed one of the five experimental diets. At the end of the experiment, final weight, weight gain, specific growth rate and feed conversion ratio of shrimp fed PRO0 and PRO2 diets were significantly improved compared to those fed PRO6 and PRO8 diets (P < 0.05). The proximate composition of muscle and the whole body indicated an increase in crude protein content with an increase in dietary PRO level. These results suggest that, for whiteleg shrimp, the optimum dietary level of PRO when used as a replacement for fish meal should be greater than 10% (PRO2) but less than 20% (PRO4) without any additional dietary amino acid supplementation.
A nonhuman primate model of early Alzheimer's disease pathologic change: Implications for disease pathogenesis
Authors: Latimer Caitlin S. , Shively Carol A. , Keene C. Dirk , Jorgensen Matthew J. , Andrews Rachel N. , Register Thomas C. , Montine Thomas J. , Wilson Angela M. , Neth Bryan J. , Mintz Akiva , Maldjian Joseph A. , Whitlow Christopher T. , Kaplan Jay R. , Craft Suzanne
Published: November 2018

Introduction

Nonhuman primates may serve as excellent models of sporadic age‐associated brain β‐amyloid deposition and Alzheimer's disease pathologic changes. We examined whether a vervet nonhuman primate model recapitulated pathologic, physiologic, and behavioral features of early Alzheimer's disease.

Methods

Nine middle‐aged (mean = 11.2 years) and nine aged (mean = 21.7 years) female vervet/African green monkeys underwent cerebrospinal fluid collection, gait speed measurement, and neuroimaging before neuropathologic assessment.

Results

β‐amyloid plaques were identified in all aged vervets and paired helical filament tau immunoreactivity was observed in all animals. Cerebrospinal fluid β‐amyloid42 and gait speed correlated negatively with age and plaque density. Greater plaque and paired helical filament tau burden predicted reduced volumes and CMRg in several brain regions.

Discussion

We observed a coordinated set of relationships among neuropathologic, cerebrospinal fluid, imaging, and behavioral modalities consistent with early Alzheimer's disease. Our results support future use of the vervet model to explore disease mechanisms, biomarkers, and novel therapeutic strategies.
Drink Beer for Science: An Experiment on Consumer Preferences for Local Craft Beer
Authors: Hart Jarrett
Published: November 2018

The U.S. and global beer industries include a great many smaller-scale craft breweries supplying numerous differentiated products as well as a few macro-breweries with less diverse beer portfolios. The craft and macro segments of this industry have become quite distinct, with little substitutability between the two types of beer. Furthermore, since the early 2000s the craft segment has realized consistent growth whereas large breweries have seen a steady decline in sales. Macro-breweries have responded by acquiring smaller breweries to capture a share of the craft market. This study implements an experimental approach to measure consumers’ willingness to pay (WTP) for locally produced and independently owned beer. Regression analysis clearly indicates that consumers prefer locally owned and independently produced beer, and how much they are willing to pay for those attributes. (JEL Classifications: D12, L66)
Terrorism and Wine Tourism: The Case of Museum Attendance
Authors: Gergaud Olivier , Livat Florine , Song Haiyan
Published: November 2018

In this article, we use attendance data from La Cité du Vin, a wine museum in the city of Bordeaux, to assess the impact of the recent wave of terror that affected France on wine tourism. We use recent count regression estimation techniques suited for time series data to build a prediction model of the demand for attendance at this museum. We conclude that the institution lost about 5,000 visitors over 426 days, during which 14 successive terrorist attacks took place. This corresponds to almost 1% of the total number of visitors in the sample period. (JEL Classifications: L83, Z30)
The Genesis of the Birther Rumor: Partisanship, Racial Attitudes, and Political Knowledge
Authors: Jardina Ashley , Traugott Michael
Published: November 2018

A growing body of work has examined the psychological underpinnings of conspiracy theory endorsement, arguing that the propensity to believe in conspiracy theories and political rumors is a function of underlying predispositions and motivated reasoning. We show, like others, that rumor endorsement can also be a function of individuals’ group attitudes. In particular, among white Americans, birther beliefs are uniquely associated with racial animus. We merge this finding with other work which shows that rumors are more strongly endorsed by the individuals most motivated and capable of integrating them among their pre-existing attitudes and beliefs. We find, therefore, that it is white Republicans who are both racially conservativeandhighly knowledgeable who possess the most skepticism about Obama's birthplace.
The utility of virtual reality surgical simulation in the undergraduate otorhinolaryngology curriculum
Authors: Hardcastle T , Wood A
Published: November 2018

Objective

To examine the impact of temporal bone virtual reality surgical simulator use in the undergraduate otorhinolaryngology curriculum.

Methods

Medical students attended a workshop involving the use of a temporal bone virtual reality surgical simulator. Students completed a pre-workshop questionnaire on career interests. A post-workshop questionnaire evaluated the perceived usefulness and enjoyment of the virtual reality surgical simulator experience, and assessed changes in their interest in ENT.

Results

Thirty-two fifth-year University of Auckland medical students were recruited. The majority of students (53.1 per cent) had already chosen their career path. The simulator experience was useful for: stimulating thoughts around career plans (71.9 per cent), providing hands-on experience (93.8 per cent) and teaching disease processes (93.8 per cent). After the workshop, 53.1 per cent of students were more interested in a career in ENT.

Conclusion

Virtual reality may be a fun and engaging way of teaching ENT. Furthermore, it could help guide student career planning.
Care Ethics and Public Policy: A Holistic, Transformative Approach
Authors: Greenswag Kari
Published: November 2018

Policy documents are a source of authority in both a legal and a normative sense. When policy documents make particular assumptions about care work requiring private, not public, consideration, this can push care, its concerns, and those who give and receive care out of the public sphere. This marginalization of care work, however, is ethically suspect, and as such I argue here that we should use the feminist ethics of care as a way to analyze current policy and guide the creation of future policy to ensure more ethically robust policy statements. I advocate for the use of care ethics in addition to human rights ethically guided public policy, which prioritizes the effort to implement human rights standards through government action. My claim is that human rights should not be our sole basis for moral and political reasoning, especially in the policy process. Policy shapes our lives, and how we live in relation to particular others. Care ethics can and should be used as an ethical guide for the policy process because it can bring to the fore how institutional patterns of power shape our relations, an analysis that human rights theories are not, in general, built to undertake.
Cohort Differences in the Association of Cardiovascular Risk and Cognitive Aging
Authors: Karlsson Peter , Johansson Boo , Skoog Ingmar , Skoog Johan , Rydén Lina , Thorvaldsson Valgeir
Published: November 2018

Abstract. Aim: To investigate birth cohort differences in associations between cardiovascular risk and fluid cognition between the age of 70 and 79. Method: Data were drawn from representative population-based cohort samples (H70), born 1901–1902, 1906–1907, and 1930, measured at ages 70, 75, and 79 on fluid cognitive measures (spatial ability and logical reasoning). The Framingham Risk Score (FRS), derived from office-based nonlaboratory predictors (age, sex, systolic blood pressure, BMI, smoking, diabetes status), was used to measure cardiovascular risk. Multiple-group latent growth curve models were fitted to the data. Findings: Estimates revealed small associations between the FRS and fluid cognition. These associations were slightly reduced in the 1930 cohort. Conclusion: Findings suggest diminishing adverse effects of cardiovascular risk on cognitive aging in cohorts born later.
VDAC2 enables BAX to mediate apoptosis and limit tumor development
Authors: Chin Hui San , Li Mark X. , Tan Iris K. L. , Ninnis Robert L. , Reljic Boris , Scicluna Kristen , Dagley Laura F. , Sandow Jarrod J. , Kelly Gemma L. , Samson Andre L. , Chappaz Stephane , Khaw Seong L. , Chang Catherine , Morokoff Andrew , Brinkmann Kerstin , Webb Andrew , Hockings Colin , Hall Cathrine M. , Kueh Andrew J. , Ryan Michael T. , Kluck Ruth M. , Bouillet Philippe , Herold Marco J. , Gray Daniel H. D. , Huang David C. S. , van Delft Mark F. , Dewson Grant
Published: November 2018

Intrinsic apoptosis is critical to prevent tumor formation and is engaged by many anti-cancer agents to eliminate tumor cells. BAX and BAK, the two essential mediators of apoptosis, are thought to be regulated through similar mechanisms and act redundantly to drive apoptotic cell death. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as important for BAX, but not BAK, to function. Genetic deletion of VDAC2 abrogated the association of BAX and BAK with mitochondrial complexes containing VDAC1, VDAC2, and VDAC3, but only inhibited BAX apoptotic function. Deleting VDAC2 phenocopied the loss of BAX in impairing both the killing of tumor cells by anti-cancer agents and the ability to suppress tumor formation. Together, our studies show that efficient BAX-mediated apoptosis depends on VDAC2, and reveal a striking difference in how BAX and BAK are functionally impacted by their interactions with VDAC2.
Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy
Authors: Geng Hao , Xue Changhui , Mendonca Janet , Sun Xiao-Xin , Liu Qiong , Reardon Patrick N. , Chen Yingxiao , Qian Kendrick , Hua Vivian , Chen Alice , Pan Freddy , Yuan Julia , Dang Sang , Beer Tomasz M. , Dai Mu-Shui , Kachhap Sushant K. , Qian David Z.
Published: November 2018

Despite recent advances, the efficacy of androgen/androgen receptor (AR)-targeted therapy remains  limited for many patients with metastatic prostate cancer. This is in part because prostate cancers adaptively switch to the androgen/AR-independent pathway for survival and growth, thereby conferring therapy resistance. Tumor hypoxia is considered as a major cause of treatment resistance. However, the exact mechanism is largely unclear. Here we report that chronic-androgen deprivation therapy (ADT) in the condition of hypoxia induces adaptive androgen/AR-independence, and therefore confers resistance to androgen/AR-targeted therapy, e.g., enzalutamide. Mechanistically, this is mediated by glucose-6-phosphate isomerase (GPI), which is transcriptionally repressed by AR in hypoxia, but restored and increased by AR inhibition. In turn, GPI maintains glucose metabolism and energy homeostasis in hypoxia by redirecting the glucose flux from androgen/AR-dependent pentose phosphate pathway (PPP) to hypoxia-induced glycolysis pathway, thereby reducing the growth inhibitory effect of enzalutamide. Inhibiting GPI overcomes the therapy resistance in hypoxia in vitro and increases enzalutamide efficacy in vivo.
National and sub-national variation in patterns of febrile case management in sub-Saharan Africa
Authors: Alegana Victor A. , Maina Joseph , Ouma Paul O. , Macharia Peter M. , Wright Jim , Atkinson Peter M. , Okiro Emelda A. , Snow Robert W. , Tatem Andrew J.
Published: November 2018

Given national healthcare coverage gaps, understanding treatment-seeking behaviour for fever is crucial for the management of childhood illness and to reduce deaths. Here, we conduct a modelling study triangulating household survey data for fever in children under the age of five years with georeferenced public health facility databases (n = 86,442 facilities) in 29 countries across sub-Saharan Africa, to estimate the probability of seeking treatment for fever at public facilities. A Bayesian item response theory framework is used to estimate this probability based on reported fever episodes, treatment choice, residence, and estimated travel-time to the nearest public-sector health facility. Findings show inter- and intra-country variation, with the likelihood of seeking treatment for fever less than 50% in 16 countries. Results highlight the need to invest in public healthcare and related databases. The variation in public sector use illustrates the need to include such modelling in future infectious disease burden estimation.
Isothermal oxidation behavior of TribaloyTM T400 and T800
Authors: Peng Jian , Fang Xufei , Marx Vera , Jasnau Ulf , Palm Martin
Published: November 2018

TribaloyTM alloys are well-known as wear-resistant alloys, however, their oxidation kinetics and mechanisms are not well studied, especially their long-term oxidation behavior. In this work, the long-term isothermal oxidation behavior of TribaloyTM T400 and T800 in synthetic air at 900 °C for up to 1000 h was investigated. The mass gains of the samples were continuously recorded during the experiments with a thermobalance. Post mortem inspection of the samples was performed and the oxidation mechanism was analyzed. The results show that T800 has a better oxidation resistance than T400. The parabolic rate constant kp of T800 is 4.9·10−14 g2·cm−4·s−1, which is approximately one order of magnitude lower than 4.8·10−13 g2·cm−4·s−1 for T400. The penetration depth of the oxides in T800 is less than half of that in T400 and steady state oxidation is attained after approximately 200 h, compared to 350 h for T400. The better oxidation resistance of T800 correlates with its higher Cr content whereby protective Cr2O3 scales form more readily.
Enhanced anti-metastatic bioactivity of an IGF-TRAP re-engineered to improve physicochemical properties
Authors: Vaniotis George , Moffett Serge , Sulea Traian , Wang Ni , Elahi S. Mehdy , Lessard Etienne , Baardsnes Jason , Perrino Stephanie , Durocher Yves , Frystyk Jan , Massie Bernard , Brodt Pnina
Published: November 2018

The insulin-like growth factor (IGF) axis has been implicated in the progression of malignant disease and identified as a clinically important therapeutic target. Several IGF-1 receptor (IGF-1R) targeting drugs including humanized monoclonal antibodies have advanced to phase II/III clinical trials, but to date, have not progressed to clinical use, due, at least in part, to interference with insulin receptor signalling. We previously reported on the production of a soluble fusion protein consisting of the extracellular domain of human IGF-1R fused to the Fc portion of human IgG1 (first generation IGF-TRAP) that bound human IGF-1 and IGF-2 with a 3 log higher affinity than insulin. We showed that the IGF-TRAP had potent anti-cancer activity in several pre-clinical models of aggressive carcinomas. Here we report on the re-engineering of the IGF-TRAP with the aim of improving physicochemical properties and suitability for clinical applications. We show that cysteine-serine substitutions in the Fc hinge region of IGF-TRAP eliminated high-molecular-weight oligomerized species, while a further addition of a flexible linker, not only improved the pharmacokinetic profile, but also enhanced the therapeutic profile of the IGF-TRAP, as evaluated in an experimental colon carcinoma metastasis model. Dose-response profiles of the modified IGF-TRAPs correlated with their bio-availability profiles, as measured by the IGF kinase-receptor-activation (KIRA) assay, providing a novel, surrogate biomarker for drug efficacy. This study provides a compelling example of structure-based re-engineering of Fc-fusion-based biologics for better manufacturability that also significantly improved pharmacological parameters. It identifies the re-engineered IGF-TRAP as a potent anti-cancer therapeutic.
Establishing a prediction model for lateral neck lymph node metastasis in patients with papillary thyroid carcinoma
Authors: Jin Shan , Bao Wuyuntu , Yang Yun-Tian , Bai Tala , Bai Yinbao
Published: November 2018

This study aimed to establish a model for predicting lateral neck lymph node metastasis in patients with papillary thyroid carcinoma. A total of 106 patients with papillary thyroid carcinoma undergoing initial treatment of neck lymph node dissection (including central and lateral neck lymph nodes) at the thyroid surgery department were enrolled from January 2009 to April 2017. Logistic regression analysis was used to screen the factors influencing lateral neck lymph node metastasis and develop a prediction model. The receiver operating characteristic curve was used to evaluate the predictive power and boundary value of the model for lateral neck lymph node metastasis. Prediction model: Logistic(P) = −5.699 + 0.681 × (TSH) + 0.342 × (Metastatic rate of central lymph nodes) + 1.463 × (Combined with Hashimoto’s disease) + 1.525 × (Number of tumors). When logistic (P) was ≥ 0.821, it was predicted that lateral neck lymph node metastasis occurred in patients with papillary thyroid carcinoma. When logistic (P) was <0.821, it was predicted that no metastasis was found in the lateral neck lymph node. The prediction accuracy was 78.3%. The model helped in evaluating lateral neck lymph node metastasis in patients with papillary thyroid carcinoma. Also, it had significance in determining reasonable surgical range, reducing unnecessary lateral neck lymph node dissection, and further improving the quality of life of patients.
Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells
Authors: Tsuma-Kaneko Mitsuyo , Sawanobori Masakazu , Kawakami Shohei , Uno Tomoko , Nakamura Yoshihiko , Onizuka Makoto , Ando Kiyoshi , Kawada Hiroshi
Published: November 2018

Although vitamin C (VC) has recently garnered interest as an alternative cancer therapy, its clinical effects remain controversial. It was recently reported using in vitro prostate cancer cell lines that excess extracellular iron (EEI) diminishes anti-cancer effects of VC, promoting the decomposition of hydrogen peroxide (H2O2) generated by VC. Here we demonstrated that EEI diminished the inhibitory effect of VC on the survival of K562 human leukemic cells in vitro, by reducing the amount of H2O2 and abrogating the apoptosis pathways induced by VC. In vivo, in the presence of EEI, the growth inhibitory effect of VC on K562 cells was completely abrogated; in fact, VC enhanced K562 cell growth. Reduction of EEI restored the apoptosis-inducing effect of VC in vitro and enhanced the growth inhibitory effect of VC in vivo. Further studies are warranted to investigate whether the combination of VC and iron depletion has similar effects in various other leukemic or cancer cells against which VC has been effective in previous experimental studies.
Total flavonoids from Semen Cuscutae target MMP9 and promote invasion of EVT cells via Notch/AKT/MAPK signaling pathways
Authors: Gao Feixia , Zhou Chun , Qiu Weiyu , Wu Haiwang , Li Jing , Peng Jinting , Qiu Min , Liang Chun , Gao Jie , Luo Songping
Published: November 2018

Miscarriage is a common condition during pregnancy and its mechanisms remain largely unknown. Extravillous trophoblast (EVT) cell invasion is required to maintain normal pregnancy and its malfunction has been proposed as a major cause for miscarriage. Homeostasis of matrix metalloproteinase 9 (MMP9) is a key to regulate EVT cell invasion. Total flavonoids from Semen Cuscutae (TFSC) have been applied clinically used for preventing or treating miscarriage in the past. Given its potential clinical benefit on preventing miscarriage, this study aims at examining the therapeutic effect of TFSC in the prevention of premature birth by upregulating MMP9 and promote EVT cell invasion. HTR-8 cells migration and invasion functions were analyzed using wound healing and transwell assays. The regulatory effect of TFSC on MMP9 expression and relevant signaling pathways were analyzed by Western Blot. The results show compared to control group, TFSC significantly promoted the migration of EVT cells in a dose and time-dependent manner. The migration and invasion of EVT cells were maximized at the highest dosage of 5 μg/ml of TFSC. The expression of MMP9 in EVT cells was significantly increased after TFSC treatment. Furthermore, cells treated with TFSC significantly upregulated protein expressions in Notch, AKT and p38/MAPK signaling pathways. We believe TFSC can promote the migration and invasion of EVT cells by increasing MMP9 expression, and prevent miscarriage by activating Notch, AKT, and MAPK signaling pathways.
HIF-2α, but not HIF-1α, mediates hypoxia-induced up-regulation of Flt-1 gene expression in placental trophoblasts
Authors: Sasagawa Tadashi , Nagamatsu Takeshi , Morita Kazuki , Mimura Nobuko , Iriyama Takayuki , Fujii Tomoyuki , Shibuya Masabumi
Published: November 2018

Placental hypoxia and elevated levels of circulating soluble Fms-like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, are closely related to the pathogenesis of preeclampsia. Although sFlt-1 secretion from the placental trophoblasts is increased under hypoxic conditions, the underlying molecular mechanism remains unclear. Previously, an authentic hypoxia response element in the Flt-1 gene promoter was shown to be a potential binding site for hypoxia-inducible factors (HIFs). Here, we investigated the roles of HIF-1α and HIF-2α in Flt-1 gene expression in trophoblast-derived choriocarcinoma cell lines and cytotrophoblasts exposed to hypoxic conditions. In the cell lines, increased expression of sFlt-1 splice variants and nuclear accumulation of HIF-1α and HIF-2α were observed after hypoxic stimulation. A specific small interfering RNA or an inhibitor molecule targeting HIF-2α decreased hypoxia-induced up-regulation of Flt-1 gene expression. Moreover, in cytotrophoblasts, increased sFlt-1 mRNA expression and elevated sFlt-1 production were induced by hypoxic stimulation. Notably, hypoxia-induced elevation of sFlt-1 secretion from the cytotrophoblasts was inhibited by silencing the HIF-2α, but not HIF-1α mRNA. These findings suggest that hypoxia-induced activation of HIF-2α is essential for the increased production of sFlt-1 proteins in trophoblasts. Targeting the HIF-2α may be a novel strategy for the treatment of preeclampsia.
Evaluation of a preclinical photon-counting CT prototype for pulmonary imaging
Authors: Kopp Felix K. , Daerr Heiner , Si-Mohamed Salim , Sauter Andreas P. , Ehn Sebastian , Fingerle Alexander A. , Brendel Bernhard , Pfeiffer Franz , Roessl Ewald , Rummeny Ernst J. , Pfeiffer Daniela , Proksa Roland , Douek Philippe , Noël Peter B.
Published: November 2018

The purpose of this study was to investigate a preclinical spectral photon-counting CT (SPCCT) prototype compared to conventional CT for pulmonary imaging. A custom-made lung phantom, including nodules of different sizes and shapes, was scanned with a preclinical SPCCT and a conventional CT in standard and high-resolution (HR-CT) mode. Volume estimation was evaluated by linear regression. Shape similarity was evaluated with the Dice similarity coefficient. Spatial resolution was investigated via MTF for each imaging system. In-vivo rabbit lung images from the SPCCT system were subjectively reviewed. Evaluating the volume estimation, linear regression showed best results for the SPCCT compared to CT and HR-CT with a root mean squared error of 21.3 mm3, 28.5 mm3 and 26.4 mm3 for SPCCT, CT and HR-CT, respectively. The Dice similarity coefficient was superior for SPCCT throughout nodule shapes and all nodule sizes (mean, SPCCT: 0.90; CT: 0.85; HR-CT: 0.85). 10% MTF improved from 10.1 LP/cm for HR-CT to 21.7 LP/cm for SPCCT. Visual investigation of small pulmonary structures was superior for SPCCT in the animal study. In conclusion, the SPCCT prototype has the potential to improve the assessment of lung structures due to higher resolution compared to conventional CT.
Waveforms of molecular oscillations reveal circadian timekeeping mechanisms
Authors: Jo Hang-Hyun , Kim Yeon Jeong , Kim Jae Kyoung , Foo Mathias , Somers David E. , Kim Pan-Jun
Published: November 2018

Circadian clocks play a pivotal role in orchestrating numerous physiological and developmental events. Waveform shapes of the oscillations of protein abundances can be informative about the underlying biochemical processes of circadian clocks. We derive a mathematical framework where waveforms do reveal hidden biochemical mechanisms of circadian timekeeping. We find that the cost of synthesizing proteins with particular waveforms can be substantially reduced by rhythmic protein half-lives over time, as supported by previous plant and mammalian data, as well as our own seedling experiment. We also find that previously enigmatic, cyclic expression of positive arm components within the mammalian and insect clocks allows both a broad range of peak time differences between protein waveforms and the symmetries of the waveforms about the peak times. Such various peak-time differences may facilitate tissue-specific or developmental stage-specific multicellular processes. Our waveform-guided approach can be extended to various biological oscillators, including cell-cycle and synthetic genetic oscillators.
High-resolution gridded soil moisture and soil temperature datasets for the Indian monsoon region
Authors: Nayak H. P. , Osuri K. K. , Sinha Palash , Nadimpalli Raghu , Mohanty U. C. , Chen Fei , Rajeevan M. , Niyogi D.
Published: November 2018

High-resolution soil moisture/temperature (SM/ST) are critical components of the growing demand for fine-scale products over the Indian monsoon region (IMR) which has diverse land-surface characteristics. This demand is fueled by findings that improved representation of land-state help improve rainfall/flood prediction. Here we report on the development of a high-resolution (4 km and 3 hourly) SM/ST product for 2001–2014 during Indian monsoon seasons (June–September). First, the quality of atmospheric fields from five reanalysis sources was examined to identify realistic forcing to a land data assimilation system (LDAS). The evaluation of developed SM/ST against observations highlighted the importance of quality forcing fields. There is a significant relation between the forcing error and the errors in the SM/ST. A combination of forcing fields was used to develop 14-years of SM/ST data. This dataset captured inter-annual, intra-seasonal, and diurnal variations under different monsoon conditions. When the mesoscale model was initialized using the SM/ST data, improved simulations of heavy rain events was evident, demonstrating the value of the data over IMR.
β-Cyclodextrin protected gold nanoparticle based cotton swabs as an effective candidate for specific sensing of trace levels of cyanide
Authors: Rajamanikandan Ramar , Ilanchelian Malaichamy
Published: November 2018

In this paper, a rapid colorimetric and easy visual determination of cyanide ions (CN− ions) in water, based on gold nanoparticles (AuNPs) stabilized with β-cyclodextrin (β-CD), is described.
Synthesis and electrochemical characterization of electroactive IoNanofluids with high dielectric constants from hydrated ferrous sulphate
Authors: Joseph Aswathy , Xavier Marylin Mary , Fal Jacek , Żyła Gaweł , Sasi Soorya , Radhakrishnan Nair P. , Padmanabhan A. S. , Mathew Suresh
Published: November 2018

An iron oxide based-electroactive IoNanofluid with a high dielectric constant, high stability and low viscosity was synthesized from ferrous sulphate heptahydrateviaa facile microwave assisted one-step route in 1-butyl-4-methylpyridinium chloride.
Binding effects in sulfur Kα and Kβ X-ray emission spectra
Authors: Sánchez E. , Torres Deluigi M. , Castellano G.
Published: November 2018

Sulfur samples in different oxidation states (+4, +6, 0 and −2) were irradiated in a commercial microscope, acquiring Kα and Kβ spectra in order to investigate the influence of the chemical bond on the occurrence of different sulfur decays to 1s vacancy states.
The interparticle distance limit for multiple exciton dissociation in PbS quantum dot solid films
Authors: Nakazawa Naoki , Zhang Yaohong , Liu Feng , Ding Chao , Hori Kanae , Toyoda Taro , Yao Yingfang , Zhou Yong , Hayase Shuzi , Wang Ruixiang , Zou Zhigang , Shen Qing
Published: November 2018

The charge transfer rate constant knet of single exciton, biexciton and triexciton within the QD solid film is exponentially enhanced as the interparticle distance between the QDs decreases, in which the charge transfer occurs via tunneling of charges between the neighboring QDs.
Electrical switching properties and structural characteristics of GeSe–GeTe films
Authors: Ren Kun , Zhu Min , Song Wenxiong , Lv Shilong , Xia Mengjiao , Wang Yong , Lu Yaoyao , Ji Zhenguo , Song Zhitang
Published: November 2018

The local structural motifs in GeSe–GeTe have been determined, which is essential to understand its thermal and electrical switching behavior.
The roles of thermally activated delayed fluorescence sensitizers for efficient red fluorescent organic light-emitting diodes with D–A–A type emitters
Authors: Wang Ya-Kun , Huang Chen-Chao , Kumar Sarvendra , Wu Sheng-Fan , Yuan Yi , Aziz Khan Aziz Khan , Jiang Zuo-Quan , Fung Man-Keung , Liao Liang-Sheng
Published: November 2018

The roles of thermally activated delayed fluorescence sensitizers (4CzIPN and OSTFCN) are investigated by developing two red D–A–A type chromophores.
Understanding the effects of vicinal carbon substituents and configuration on organofluorine hydrogen-bonding interaction
Authors: Jia Qingqing , Li Qingzhong , Luo Mo , Li Hai-Bei
Published: November 2018

The vicinal substituents, with gauche/stagger isomer in CH2XCH2F and cis/trans isomer in CHXCHF, affect the interaction of C(spn)–F⋯H–O organofluorine hydrogen bonds differently.
Synthesis and biological study of acridine-based imidazolium salts
Authors: Sharhan Olla , Heidelberg Thorsten , Hashim Najiahah Mohd , Salman Abbas Abdulameer , Ali Hapipah Mohd , Jayash Soher Nagi
Published: November 2018

A series of acridine-based imidazolium salts was synthesized and studied on cytotoxicity against human cancer cell lines.