bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment strategies for recurrent and residual aneurysms after Woven Endobridge implantation
Authors: Kabbasch Christoph , Goertz Lukas , Siebert Eberhard , Herzberg Moriz , Hamisch Christina , Mpotsaris Anastasios , Dorn Franziska , Liebig Thomas
Published: August 2018

Background

Woven Endobridge (WEB) embolization is a safe and efficient technique for endovascular treatment of intracranial aneurysms. However, the management of aneurysm recurrence after WEB placement has not been well described to date. We present our multicenter experience of endovascular retreatment of aneurysm recurrence after WEB implantation.

Methods

This is a multicenter study of patients who underwent endovascular retreatment after WEB implantation in three German tertiary care centers. Treatment strategies, complications, and angiographic outcome were retrospectively assessed.

Results

Among 122 aneurysms treated with the WEB device, 15 were retreated. Of these, six were initially treated with the WEB only, two were pretreated by coiling, and seven large aneurysms were treated in a multimodality approach. Ten were true aneurysm remnants and five were neck remnants. The reasons for retreatment were WEB migration (n=6), initial incomplete occlusion (n=5), and WEB compression (n=4). Retreatment strategies included coiling (n=4), stent-assisted coiling (n=7), flow diversion (n=3), and placement of an additional WEB (n=1). All procedures were technically successful and there were no procedure-related complications. Among 11 patients available for follow-up after retreatment, three were retreated again. At last angiographic follow-up, available in 11/15 cases at a median of 23 months, complete occlusion was obtained in eight cases and neck remnants in three.

Conclusions

This pilot study shows that endovascular retreatment of recurrent or residual aneurysms after WEB implantation can be done safely and can achieve adequate occlusion rates.
AptimaTrichomonas vaginalisassay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study
Authors: Bruni Mirian Pinheiro , Freitas da Silveira Mariangela , Stauffert Dulce , Bicca Guilherme Lucas de Oliveira , Caetano dos Santos Carolina , da Rosa Farias Nara Amélia , Golparian Daniel , Unemo Magnus
Published: August 2018

Objectives

Trichomonas vaginalis (TV) infection is the most common non-viral STI globally and can result in adverse pregnancy outcomes and exacerbated HIV acquisition/transmission. Nucleic acid amplification tests (NAATs) are the most sensitive diagnostic tests, with high specificity, but TV NAATs are rarely used in Brazil. We investigated the TV prevalence and compared the performance of the US Food and Drug Association-cleared Aptima TV assay with microscopy (wet mount and Gram-stained) and culture for TV detection in women in Pelotas, Brazil in an observational study.

Methods

From August 2015 to December 2016, 499 consecutive asymptomatic and symptomatic sexually active women attending a Gynaecology and Obstetrics Outpatient Clinic were enrolled. Vaginal fluid and swab specimens were collected and wet mount microscopy, Gram-stained microscopy, culture and the Aptima TV assay performed.

Results

The median age of enrolled women was 36.5 years (range: 15–77). The majority were white, had a steady sexual partner and low levels of education. The TV detection rate was 4.2%, 2.4%, 1.2% and 0% using the Aptima TV assay, culture, wet mount microscopy and Gram-stained microscopy, respectively. The sensitivity of culture and wet mount microscopy was only 57.1% (95% CI 36.5 to 75.5) and 28.6% (95% CI 13.8 to 50.0), respectively.

Conclusions

A 4.2% positivity rate ofT. vaginaliswas found among women in Pelotas, Brazil and the routine diagnostic test (wet mount microscopy) and culture had low sensitivities. More sensitive diagnostic tests (NAATs) and enhanced testing of symptomatic and asymptomatic at-risk women are crucial to mitigate the transmission of TV infection, TV-associated sequelae and enhanced HIV acquisition and transmission.
Effects of different vehiculization strategies for the allium derivative propyl propane thiosulfonate during dynamic simulation of the pig gastrointestinal tract
Authors: Abad Paloma , Arroyo-Manzanares Natalia , Rivas-Montoya E. , Ochando-Pulido J.M. , Guillamon Enrique , García-Campaña Ana M. , Martinez-Ferez Antonio
Published: August 2018

This paper evaluates the bioavailability of allium derivative propyl propane thiosulfonate (PTSO) in the pig gastrointestinal tract by means of an in vitro dynamic gastrointestinal tract simulator system (GITSS). The GITSS is based on a membrane bioreactor comprising a continuous stirred-tank reactor connected in series to a continuous plug-flow tubular reactor. Bioavailability values have been evaluated for different vehiculization strategies, including mere carriers such as polyethylene glycol sorbitan monooleate (a nonionic surfactant also known as Tween 80) and encapsulation matrices (β-cyclodextrin vs. mono- and di-glycerides of edible fatty acids mixed with hydrogenated sunflower oil) and compared with the absorption of free PTSO. The net absorbed amount of PTSO in the GITSS when Tween 80 was used as a carrier was over 3.5 times higher than the one for free PTSO. Neither the encapsulated PTSO in β-cyclodextrin nor by means of mono- and di-glycerides of fatty acids plus a vegetable oil succeeded to improve absorption values for free PTSO. These promising results indicate that Tween 80 provides an interesting and high resistance to the PTSO molecule against the simulated digestive conditions in the stomach, and thus it enables favorably the subsequent absorption process of PTSO along the intestine.
Comment on “Collision strength and effective collision strength for Ba XLVIII” by Mohan et al. [Can. J. Phys. 95, 173 (2017)]
Authors: Aggarwal Kanti M.
Published: August 2018

In a recent paper, Mohan et al. [Can. J. Phys. 95, 173 (2017)] have reported results for collision strengths (Ω) and effective collision strengths (ϒ) for transitions from the ground to higher 51 excited levels of F-like Ba XLVIII. For the calculations of Ω, the Dirac atomic R-matrix code (DARC) and the flexible atomic code (FAC) have been adopted, to facilitate a direct comparison. However, for the subsequent calculations of ϒ, DARC alone has been employed. In this comment, we demonstrate that while their limited results for Ω are comparatively reliable, for ϒ they are not, particularly for the allowed transitions and at lower temperatures. Apart from the unexpected behaviour, their ϒ values are overestimated for several transitions, by about a factor of two.
Antrolone, a Novel Benzoid Derived from Antrodia cinnamomea, Inhibits the LPS-Induced Inflammatory Response in RAW264.7 Macrophage Cells by Balancing the NF-κB and Nrf2 Pathways
Authors: Yen I-Chuan , Shi Li-Shian , Chung Min-Chieh , Ahmetaj-Shala Blerina , Chang Tsu-Chung , Lee Shih-Yu
Published: August 2018

Antrodia cinnamomea, a medicinal mushroom, has previously demonstrated anti-inflammatory activity, although the specific compound responsible for the effect remains unclear. The present study was designed to investigate the anti-inflammatory property of antrolone, a novel benzoid derived from A. cinnamomea mycelium, and to clarify the underlying mechanisms of action. To this end, murine macrophage RAW264.7 cells were treated with antrolone (0.1–30[Formula: see text][Formula: see text]M) 30[Formula: see text]min prior to stimulation with lipopolysaccharides (LPS, 0.1[Formula: see text][Formula: see text]g/ml) for 24[Formula: see text]h. Cell viability, nitric oxide (NO) and prostaglandin E2 (PGE2) production, levels of pro-inflammatory cytokines and chemokines, and the signaling pathways involved in the inflammatory cascades were then investigated. Our results show that antrolone significantly decreased LPS-induced NO, PGE2, pro-inflammatory cytokine, and keratinocyte chemoattractant CXCL1 (KC) production and reduced levels of the proteins inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). These effects were independent of the effect of antrolone on macrophage cytotoxicity. Moreover, antrolone significantly inhibited the activation of the NF[Formula: see text]B, MAPK, and AKT pathways, while it increased nuclear factor erythroid-2-related factor (Nrf2) and heme oxygenase-1 (HO-1) levels. Our findings suggest that antrolone exhibits potent anti-inflammatory activity and may, therefore, be a lead compound for the development of an anti-inflammatory drug.
Genome-Wide Methylation Analysis Identifies NOX4 and KDM5A as Key Regulators in Inhibiting Breast Cancer Cell Proliferation by Ginsenoside Rg3
Authors: Ham Juyeon , Lee Seungyeon , Lee Hyunkyung , Jeong Dawoon , Park Sungbin , Kim Sun Jung
Published: August 2018

Ginsenoside Rg3 is a key metabolite of ginseng and is known to inhibit cancer cell growth. However, the epigenetics of CpG methylation and its regulatory mechanism have yet to be determined. Genome-wide methylation analysis of MCF-7 breast cancer cells treated with Rg3 was performed to identify epigenetically regulated genes and pathways. The effect of Rg3 on apoptosis and cell proliferation was examined by a colony formation assay and a dye-based cell proliferation assay. The association between methylation and gene expression was monitored by RT-PCR and Western blot analysis. Genome-wide methylation analysis identified the “cell morphology”-related pathway as the top network. Rg3 induced late stage apoptosis but inhibited cell proliferation up to 60%. Hypermethylated TRMT1L, PSMC6 and NOX4 were downregulated by Rg3, while hypomethylated ST3GAL4, RNLS and KDM5A were upregulated. In accordance, downregulation of NOX4 by siRNA abrogated the cell growth effect of Rg3, while the effect was opposite for KDM5A. Notably, breast cancer patients with a higher expression of NOX4 and KDM5A showed poor and good prognosis of survival, respectively. In conclusion, Rg3 deregulated tumor-related genes through alteration of the epigenetic methylation level leading to growth inhibition of cancer cells.
On H-simple not necessarily associative algebras
Authors: Gordienko A. S.
Published: August 2018

An algebra [Formula: see text] with a generalized [Formula: see text]-action is a generalization of an [Formula: see text]-module algebra where [Formula: see text] is just an associative algebra with [Formula: see text] and a relaxed compatibility condition between the multiplication in [Formula: see text] and the [Formula: see text]-action on [Formula: see text] holds. At first glance, this notion may appear too general, however, it enables to work with algebras endowed with various kinds of additional structures (e.g. comodule algebras over Hopf algebras, graded algebras, algebras with an action of a semigroup by anti-endomorphisms). This approach proves to be especially fruitful in the theory of polynomial identities. We show that if [Formula: see text] is a finite dimensional (not necessarily associative) algebra over a field of characteristic [Formula: see text] and [Formula: see text] is simple with respect to a generalized [Formula: see text]-action, then there exists [Formula: see text] where [Formula: see text] is the sequence of codimensions of polynomial [Formula: see text]-identities of [Formula: see text]. In particular, if [Formula: see text] is a finite dimensional (not necessarily group graded) graded-simple algebra, then there exists [Formula: see text] where [Formula: see text] is the sequence of codimensions of graded polynomial identities of [Formula: see text]. In addition, we study the free-forgetful adjunctions corresponding to (not necessarily group) gradings and generalized [Formula: see text]-actions.
Heterogenization of manganese porphyrin via hydrogen bond in zeolite imidazolate framework-8 matrix, a host–guest interaction, as catalytic system for olefin epoxidation
Authors: Bagherzadeh Mojtaba , Mesbahi Elnaz
Published: August 2018

A heterogenized meso-tetrakis(2,3-dihydroxyphenyl)porphyrinatomanganese(III) acetate at zeolite imidazolate framework-8 (T(2,3-OHP)PorMn@ZIF-8) is investigated for the catalytic olefin epoxidation reactions at room temperature. Heterogenization is accomplished through a non-classical hydrogen bond proposed between T(2,3-OHP)PorMn bearing O–H groups and C–H of the 2-methylimidazolate linkers in the ZIF-8 structure. The aforementioned compound is characterized by X-ray powder diffraction (XRD), atomic absorption spectroscopy (AAS), nitrogen adsorption−desorption, FT-IR spectroscopy, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The catalytic system with rather high potential of reusability is proposed as a fairly efficient epoxidation catalyst compared to reports in homogeneous media.
DNA computing over the ring ℤ4[v]/〈v2 − v〉
Authors: Kumar Narendra , Singh Abhay Kumar
Published: August 2018

In this paper, we discuss the DNA construction of general length over the finite ring [Formula: see text], with [Formula: see text], which plays a very significant role in DNA computing. We discuss the GC weight of DNA codes over [Formula: see text]. Several examples of reversible cyclic codes over [Formula: see text] are provided, whose [Formula: see text]-images are [Formula: see text]-linear codes with good parameters.
Properties of ϕ-δ-primary and 2-absorbing δ-primary ideals of commutative rings
Authors: Jaber Ameer
Published: August 2018

Let [Formula: see text] be a commutative ring with unity [Formula: see text] and let [Formula: see text] be an ideal expansion. In the first part of this paper, we extend the concept of [Formula: see text]-primary ideals to [Formula: see text]-[Formula: see text]-primary ideals, where [Formula: see text] is an ideal reduction and [Formula: see text] is an ideal expansion. We introduce some of the ideal expansion [Formula: see text] and define [Formula: see text]-[Formula: see text]-primary ideals, where [Formula: see text] is an ideal reduction. Also, we investigate ideal expansions satisfying some additional conditions and prove more properties of the generalized [Formula: see text]-[Formula: see text]-primary ideals with respect to such an ideal expansion [Formula: see text]. In the second part of this paper we investigate 2-absorbing [Formula: see text]-primary ideals which unify 2-absorbing ideals and 2-absorbing primary ideals, where [Formula: see text] is an ideal expansion. A number of results in the two parts are given.
Efficient brownfield optimization of a reservoir in west Siberia
Authors: Ushmaev O. S. , Babin V. M. , Glavnov N. G. , Yaubatyrov R. R. , Echeverría Ciaurri D. , Golitsyna M. V. , Pozdneev A. V. , Semenikhin A. S.
Published: August 2018

In this work we present a methodology for optimal management of brownfields that is illustrated on a real field. The approach does not depend on the particular reservoir flow simulator used, although streamline-derived information is leveraged to accelerate the optimization. The method allows one to include (non-linear) constraints (e.g. a recovery factor larger than a given baseline value), which are very often challenging to address with optimization tools. We rely on derivative-free optimization coupled with the filter method for non-linear constraints, although the methodology can also be combined with approaches that utilize exact/approximate gradients. Performance in terms of wall-clock time can be improved further if distributed-computing resources are available (the method is amenable to parallel implementation). The methodology is showcased using a real field in west Siberia where net present value (NPV) is maximized subject to a constraint for the recovery factor. The optimization variables represent a discrete time series for well bottom-hole pressure over a fraction of the production time frame. An increase in NPV of 7.9% is obtained with respect to an existing baseline. The optimization methods studied include local optimization algorithms (e.g. generalized pattern search) and global search procedures (e.g. particle swarm optimization). The controls for one injection well in the real field were actually modified according to the solution determined in this work. The results obtained suggest improvement for most economic scenarios.
Hyperspectral Sensors and Imaging Technologies in Phytopathology: State of the Art
Authors: Mahlein A.-K. , Kuska M.T. , Behmann J. , Polder G. , Walter A.
Published: August 2018

Plant disease detection represents a tremendous challenge for research and practical applications. Visual assessment by human raters is time-consuming, expensive, and error prone. Disease rating and plant protection need new and innovative techniques to address forthcoming challenges and trends in agricultural production that require more precision than ever before. Within this context, hyperspectral sensors and imaging techniques—intrinsically tied to efficient data analysis approaches—have shown an enormous potential to provide new insights into plant-pathogen interactions and for the detection of plant diseases. This article provides an overview of hyperspectral sensors and imaging technologies for assessing compatible and incompatible plant-pathogen interactions. Within the progress of digital technologies, the vision, which is increasingly discussed in the society and industry, includes smart and intuitive solutions for assessing plant features in plant phenotyping or for making decisions on plant protection measures in the context of precision agriculture.
Advances in Wheat and Pathogen Genomics: Implications for Disease Control
Authors: Keller Beat , Wicker Thomas , Krattinger Simon G.
Published: August 2018

The gene pool of wheat and its wild and domesticated relatives contains a plethora of resistance genes that can be exploited to make wheat more resilient to pathogens. Only a few of these genes have been isolated and studied at the molecular level. In recent years, we have seen a shift from classical breeding to genomics-assisted breeding, which makes use of the enormous advancements in DNA sequencing and high-throughput molecular marker technologies for wheat improvement. These genomic advancements have the potential to transform wheat breeding in the near future and to significantly increase the speed and precision at which new cultivars can be bred. This review highlights the genomic improvements that have been made in wheat and its pathogens over the past years and discusses their implications for disease-resistance breeding.
Effect of metformin and flutamide on insulin, lipogenic and androgen-estrogen signaling, and cardiometabolic risk in a PCOS-prone metabolic syndrome rodent model
Authors: Kupreeva M. , Diane A. , Lehner R. , Watts R. , Ghosh M. , Proctor S. , Vine D.
Published: August 2018

Polycystic ovary syndrome (PCOS) is highly associated with cardiometabolic risk and the metabolic syndrome (MetS), predisposing women to increased risk of developing type 2 diabetes and cardiovascular disease. Metformin is commonly used to treat insulin resistance-glucose intolerance, and flutamide, an androgen receptor (AR) antagonist, is used to target hyperandrogenemia and dyslipidemia. Currently, the physiological mechanism of action of these treatments on androgen, lipidogenic, and insulin signaling pathways remains unclear in PCOS. The aim of this study was to investigate the effects and mechanisms of action of metformin and flutamide on plasma lipid-apolipoprotein (Apo)B-lipoprotein and insulin-glucose metabolism, and endocrine-reproductive indices in a PCOS-prone MetS rodent model. PCOS-prone rodents were treated with metformin (300 mg/kg body wt), flutamide (30 mg/kg body wt), or metformin + flutamide combination treatment for 6 wk. Metformin was shown to improve fasting insulin and HOMA-IR, whereas flutamide and combination treatment were shown to reduce plasma triglycerides, ApoB48, and ApoB100, and this was associated with decreased intestinal secretion of ApoB48/triglyceride. Flutamide and metformin were shown to reduce plasma androgen indices and to improve ovarian primary and preovulatory follicle frequency. Metformin treatment increased hepatic estrogen receptor (ER)α, and metformin-flutamide decreased intestinal AR and increased ERα mRNA expression. Metformin-flutamide treatment upregulated hepatic and intestinal insulin signaling, including insulin receptor, MAPK1, and AKT2. In conclusion, cardiometabolic risk factors, in particular ApoB-hypertriglyceridemia, are independently modulated via the AR, and understanding the contribution of AR and insulin-signaling pathways further may facilitate the development of targeted interventions in high-risk women with PCOS and MetS.
MicroRNA-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction
Authors: Syed Maryam , Ball Jana P. , Mathis Keisa W. , Hall Michael E. , Ryan Michael J. , Rothenberg Marc E. , Yanes Cardozo Licy L. , Romero Damian G.
Published: August 2018

Primary aldosteronism is characterized by excess aldosterone secretion by the adrenal gland independent of the renin-angiotensin system and accounts for ~10% of hypertensive patients. Excess aldosterone causes cardiac hypertrophy, fibrosis, inflammation, and hypertension. The molecular mechanisms that trigger the onset and progression of aldosterone-mediated cardiac injury remain incompletely understood. MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that have been implicated in multiple cardiac pathologies; however, their regulation and role in aldosterone-mediated cardiac injury and dysfunction remains mostly unknown. We previously reported that microRNA-21 (miR-21) is the most upregulated miRNA by excess aldosterone in the left ventricle in a rat experimental model of primary aldosteronism. To elucidate the role of miR-21 in aldosterone-mediated cardiac injury and dysfunction, miR-21 knockout mice and their wild-type littermates were treated with aldosterone infusion and salt in the drinking water for 2 or 8 wk. miR-21 genetic ablation exacerbated aldosterone/salt-mediated cardiac hypertrophy and cardiomyocyte cross-sectional area. Furthermore, miR-21 genetic ablation increased the cardiac expression of fibrosis and inflammation markers and fetal gene program. miR-21 genetic ablation increased aldosterone/salt-mediated cardiac dysfunction but did not affect aldosterone/salt-mediated hypertension. miR-21 target gene Sprouty 2 may be implicated in the cardiac effects of miR-21 genetic ablation. Our study shows that miR-21 genetic ablation exacerbates aldosterone/salt-mediated cardiac hypertrophy, injury, and dysfunction blood pressure independently. These results suggest that miR-21 plays a protective role in the cardiac pathology triggered by excess aldosterone. Furthermore, miR-21 supplementation may be a novel therapeutic approach to abolish or mitigate excess aldosterone-mediated cardiovascular deleterious effects in primary aldosteronism.
Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action
Authors: Svensson Kristoffer , Dent Jessica R. , Tahvilian Shahriar , Martins Vitor F. , Sathe Abha , Ochala Julien , Patel Mulchand S. , Schenk Simon
Published: August 2018

The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is an important control point for carbohydrate (CHO) oxidation. However, the importance of the PDC and CHO oxidation to muscle metabolism and exercise performance, particularly during prolonged or high-intensity exercise, has not been fully defined especially in mature skeletal muscle. To this end, we determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 1 ( Pdha1), which is a critical subunit of the PDC, impacts resting energy metabolism, exercise performance, or metabolic adaptation to high-fat diet (HFD) feeding. For this, we generated a tamoxifen (TMX)-inducible Pdha1 knockout (PDHmKO) mouse, in which PDC activity is temporally and specifically ablated in adult skeletal muscle. We assessed energy expenditure, ex vivo muscle contractile performance, and endurance exercise capacity in PDHmKO mice and wild-type (WT) littermates. Additionally, we studied glucose homeostasis and insulin sensitivity in muscle after 12 wk of HFD feeding. TMX administration largely ablated PDHα in skeletal muscle of adult PDHmKO mice but did not impact energy expenditure, muscle contractile function, or low-intensity exercise performance. Additionally, there were no differences in muscle insulin sensitivity or body composition in PDHmKO mice fed a control or HFD, as compared with WT mice. However, exercise capacity during high-intensity exercise was severely impaired in PDHmKO mice, in parallel with a large increase in plasma lactate concentration. In conclusion, although skeletal muscle PDC is not a major contributor to resting energy expenditure or long-duration, low-intensity exercise performance, it is necessary for optimal performance during high-intensity exercise.
GlutathioneS-transferase P deficiency induces glucose intolerance via JNK-dependent enhancement of hepatic gluconeogenesis
Authors: Ghosh Dastidar Shubha , Jagatheesan Ganapathy , Haberzettl Petra , Shah Jasmit , Hill Bradford G. , Bhatnagar Aruni , Conklin Daniel J.
Published: August 2018

Hepatic glutathione S-transferases (GSTs) are dysregulated in human obesity, nonalcoholic fatty liver disease, and diabetes. The multifunctional GST pi-isoform (GSTP) catalyzes the conjugation of glutathione with acrolein and inhibits c-Jun NH2-terminal kinase (JNK) activation. Herein, we tested whether GSTP deficiency disturbs glucose homeostasis in mice. Hepatic GST proteins were downregulated by short-term high-fat diet in wild-type (WT) mice concomitant with increased glucose intolerance, JNK activation, and cytokine mRNAs in the liver. Genetic deletion of GSTP did not affect body composition, fasting blood glucose levels, or insulin levels in mice maintained on a normal chow diet; however, compared with WT mice, the GSTP-null mice were glucose intolerant. In GSTP-null mice, pyruvate intolerance, reflecting increased hepatic gluconeogenesis, was accompanied by elevated levels of activated JNK, cytokine mRNAs, and glucose-6-phosphatase proteins in the liver. Treatment of GSTP-null mice with the JNK inhibitor 1,9-pyrazoloanthrone (SP600125) significantly attenuated pyruvate-induced hepatic gluconeogenesis and significantly altered correlations between hepatic cytokine mRNAs and metabolic outcomes in GSTP-null mice. Collectively, these findings suggest that hepatic GSTP plays a pivotal role in glucose handling by regulating JNK-dependent control of hepatic gluconeogenesis. Thus, hepatic GSTP-JNK dysregulation may be a target of new therapeutic interventions during early stages of glucose intolerance to prevent the worsening metabolic derangements associated with human obesity and its relentless progression to diabetes.
A Residual Theorem Approach Applied to Stokes’ Problems with Generally Periodic Boundary Conditions including a Pressure Gradient Term
Authors: Durante Danilo , Broglia Riccardo
Published: August 2018

The differential problem given by a parabolic equation describing the purely viscous flow generated by a constant or an oscillating motion of a boundary is the well-known Stokes’ problem. The one-dimensional equation is generally solved for unbounded or bounded domains; for the latter, either free slip (i.e., zero normal gradient) or no-slip (i.e., zero velocity) conditions are enforced on one boundary. Generally, the analytical strategy to solve these problems is based on finding the solutions of the Laplace-transformed (in time) equation and on inverting these solutions. In the present paper this problem is solved by making use of the residuals theorem; as it will be shown, this strategy allows achieving the solutions of First and Second Stokes’ problems in both infinite and finite depth. The extension to generally periodic boundaries with the presence of a periodic pressure gradient is also presented. This approach allows getting closed form solutions in the time domain in a rather fast and simple way. An ad hoc numerical algorithm, based on a finite difference approximation of the differential equation, has been developed to check the correctness of the analytical solutions.
The Hierarchies of Multivalued Attribute Domains and Corresponding Applications in Data Mining
Authors: Lei Yuxia , Yan Yushu , Han Yonghua , Jiang Feng
Published: August 2018

In mobile computing, machine learning models for natural language processing (NLP) have become one of the most attractive focus areas in research. Association rules among attributes are common knowledge patterns, which can often provide potential and useful information such as mobile users′ interests. Actually, almost each attribute is associated with a hierarchy of the domain. Given an relation R = (U, A) and any cut αa on the hierarchy for every attribute a, there is another rough relation RΦ, where Φ = (αa : a ∈ A). This paper will establish the connection between the functional dependencies in R and RΦ, propose the method for extracting reducts in RΦ, and demonstrate the implementation of proposed method on an application in data mining of association rules. The method for acquiring association rules consists of the following three steps: (1) translating natural texts into relations, by NLP; (2) translating relations into rough ones, by attributes analysis or fuzzy k‐means (FKM) clustering; and (3) extracting association rules from concept lattices, by formal concept analysis (FCA). Our experimental results show that the proposed methods, which can be applied directly to regular mobile data such as healthcare data, improved quality, and relevance of rules.
Adjuvant Therapy Using Mistletoe Containing Drugs Boosts the T‐Cell‐Mediated Killing of Glioma Cells and Prolongs the Survival of Glioma Bearing Mice
Authors: Schötterl Sonja , Huber Stephan M. , Lentzen Hans , Mittelbronn Michel , Naumann Ulrike
Published: August 2018

Viscum album L. extracts (VE) are applied as complementary cancer therapeutics for more than one century. Extracts contain several compounds like mistletoe lectins (ML) 1‐3 and viscotoxins, but also several minor ingredients. Since ML‐1 has been described as one of the main active components harboring antitumor activity, purified native or recombinant ML‐1 has been also used in clinical trials in the last years. The present study examined and compared the immunoboosting effects of three ML‐1 containing drugs (the extract ISCADOR Qu, the recombinant ML‐1 Aviscumine, and purified native ML‐1) in the context of the T‐cell mediated killing of glioma cells. Additionally we examined the possible underlying T‐cell stimulating mechanisms. Using cocultures of immune and glioma cells, a PCR‐based microarray, quantitative RT‐PCR, and an antibody‐based array to measure cytokines in blood serum, immunosupporting effects were determined. A highly aggressive, orthotopic, immunocompetent syngeneic mouse glioma model was used to determine the survival of mice treated with ISCADOR Qu alone or in combination with tumor irradiation and temozolomide (TMZ). Treatment of glioblastoma (GBM) cells with ISCADOR Qu that contains a high ML concentration, but also viscotoxins and other compounds, as well as with Aviscumine or native ML‐1, enhanced the expansion of cancer cell‐specific T‐cells as well as T‐cell‐mediated tumor cell lysis, but to a different degree. In GBM cells all three ML‐1‐containing preparations modulated the expression of immune response associated genes. In vivo, subcutaneous ISCADOR Qu injections at increasing concentration induced cytokine release in immunocompetent VM/Dk‐mice. Finally, ISCADOR Qu, if applied in combination with tumor irradiation and TMZ, further prolonged the survival of glioma mice. Our findings indicate that ML‐1 containing drugs enhance anti‐GBM immune responses and work in synergy with radiochemotherapy. Therefore, adjuvant mistletoe therapy should be considered as an auspicious treatment option for glioma patients.
Investigation of Lake Hévíz Mineral Water Balneotherapy and Hévíz Mud Treatment in Murine Osteoarthritis and Rheumatoid Arthritis Models
Authors: Tékus V. , Borbély É. , Kiss T. , Perkecz A. , Kemény Á. , Horváth J. , Kvarda A. , Pintér E.
Published: August 2018

Arthritic diseases are the most frequent causes of chronic pain and disability. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and progressive structural joint damage. Osteoarthritis is a degenerative process of the articular cartilage associated with hypertrophic changes in the bone. The aim of the present study was to investigate the anti‐inflammatory and analgesic effects of Hévíz thermal water and mud in monosodium iodoacetate‐ (MIA‐) (25 mg/ml, 20 μl i.a.) induced osteoarthritis and Complete Freund’s adjuvant‐ (CFA‐) (1 mg/ml, 50–50 μl s.c) induced rheumatoid arthritis murine models. The mechanonociceptive threshold of female NMRI mice (n=6– 8 mice/ group) was measured by aesthesiometry, and paw volume was monitored with plethysmometry, knee joint diameter with digital micrometer, and dynamic weight bearing on the hind limbs with a Bioseb instrument. Periarticular bone destruction was assessed by SkyScan 1176 in vivo micro‐CT. Inflammatory cytokines were detected by ELISA in plasma samples. Treatments (30 min, every working day) with tap water, sand, and a combined therapy of tap water and sand served as controls. Hévíz medicinal water and combined treatment with water and mud significantly decreased the mechanical hyperalgesia and knee oedema in MIA‐induced osteoarthritis model. However, balneotherapy did not influence mechanical hyperalgesia, weight bearing, or oedema formation induced by CFA. Neither medicinal water nor mud treatment ameliorated deep structural damage of the bones or the joints in the animal models. On the basis of the present findings, we conclude that balneotherapy is an effective complementary treatment to reduce the pain sensation and swelling in degenerative joint diseases such as osteoarthritis. Our experimental data are in agreement with the previous human studies that also confirmed antinociceptive and anti‐inflammatory effects of thermal water and Hévíz mud treatments.
Evolution and Expression Divergence of E2 Gene Family under Multiple Abiotic and Phytohormones Stresses inBrassica rapa
Authors: Khan Nadeem , Hu Chun-mei , Amjad Khan Waleed , Naseri Emal , Ke Han , Huijie Dong , Hou Xilin
Published: August 2018

To understand ubiquitination mechanism, E2s (ubiquitin conjugating enzymes) have crucial part as they play a major role in regulating many biological processes in plants. Meanwhile,Brassica rapais an important leafy vegetable crop and therefore its characterization along with the expression pattern of E2s under various stresses is imperative. In this study, a total of 83 genes were identified inB. rapaand were classified into four different classes based on domain information. Here, we analyzed phylogenetic relationships, collinear correlation, gene duplication, interacting network, and expression patterns ofE2genes inB. rapa. Furthermore, RT-PCR analysis for 8 multiple abiotic and hormone treatments (namely, ABA, GA, JA, BR, PEG, NaCl, and heat and cold stress) illustrated striking expression pattern under one or more treatments, speculating that these might be stress-responsive genes. Thecis-elements and interaction network analyses implicate valuable clues of important function ofE2genes in development and multiple stress responses inB. rapa. This study will further facilitate functional analysis of E2s for improving stress resistance mechanism inB.rapa.
New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic Processes: The Role of Chronic Inflammation and Oxidative Stress
Authors: Georgescu Simona Roxana , Mitran Cristina Iulia , Mitran Madalina Irina , Caruntu Constantin , Sarbu Maria Isabela , Matei Clara , Nicolae Ilinca , Tocut Sandra Milena , Popa Mircea Ioan , Tampa Mircea
Published: August 2018

Human papillomavirus (HPV) is a small double-stranded DNA virus with tropism for epithelial cells. To this date, over 150 genotypes are known and are classified into two major groups, low-risk and high-risk strains, depending on the ability of the virus to induce malignant transformation. The host’s immunity plays a central role in the course of the infection; therefore, it may not be clinically manifest or may produce various benign or malignant lesions. The pathogenic mechanisms are complex and incompletely elucidated. Recent research suggests the role of chronic inflammation and oxidative stress (OS) in the pathogenesis of HPV infection and the associated carcinogenic processes. Chronic inflammation induces OS, which in turn promotes the perpetuation of the inflammatory process resulting in the release of numerous molecules which cause cell damage. Reactive oxygen species exert a harmful effect on proteins, lipids, and nucleic acids. Viral oncogenes E5, E6, and E7 are involved in the development of chronic inflammation through various mechanisms. In addition, HPV may interfere with redox homeostasis of host cells, inducing OS which may be involved in the persistence of the infection and play a certain role in viral integration and promotion of carcinogenesis. Knowledge regarding the interplay between chronic inflammation and OS in the pathogenesis of HPV infection and HPV-induced carcinogenesis has important consequences on the development of new therapeutic strategies.
A Hybrid Simulated Annealing/Linear Programming Approach for the Cover Printing Problem
Authors: Alonso-Pecina Federico , Romero David
Published: August 2018

TheNP-hard cover printing problem addressed here consists in determining the number and composition of equal size impression grids, as well as the number of times each grid is printed, in order to fulfill the demand of different book covers at minimum total printing cost. The considered costs come from printing sheets and for composing grids. Thus, to deal with this combinatorial optimization problem we investigated two heuristics: one combines simulated annealing and linear programming techniques and the other is a hybrid of Tabu Search and an ad hoc procedure. Through intensive testing on available instances, these algorithms proved to be superior to previous approaches.
Hardware/Software Adaptive Cryptographic Acceleration for Big Data Processing
Authors: Xiao Chunhua , Zhang Lei , Xie Yuhua , Liu Weichen , Liu Duo
Published: August 2018

Along with the explosive growth of network data, security is becoming increasingly important for web transactions. The SSL/TLS protocol has been widely adopted as one of the effective solutions for sensitive access. Although OpenSSL could provide a freely available implementation of the SSL/TLS protocol, the crypto functions, such as symmetric key ciphers, are extremely compute-intensive operations. These expensive computations through software implementations may not be able to compete with the increasing need for speed and secure connection. Although there are lots of excellent works with the objective of SSL/TLS hardware acceleration, they focus on the dedicated hardware design of accelerators. Hardly of them presented how to utilize them efficiently. Actually, for some application scenarios, the performance improvement may not be comparable with AES-NI, due to the induced invocation cost for hardware engines. Therefore, we proposed the research to take full advantages of both accelerators and CPUs for security HTTP accesses in big data. We not only proposed optimal strategies such as data aggregation to advance the contribution with hardware crypto engines, but also presented an Adaptive Crypto System based on Accelerators (ACSA) with software and hardware codesign. ACSA is able to adopt crypto mode adaptively and dynamically according to the request character and system load. Through the establishment of 40 Gbps networking on TAISHAN Web Server, we evaluated the system performance in real applications with a high workload. For the encryption algorithm 3DES, which is not supported in AES-NI, we could get about 12 times acceleration with accelerators. For typical encryption AES supported by instruction acceleration, we could get 52.39% bandwidth improvement compared with only hardware encryption and 20.07% improvement compared with AES-NI. Furthermore, the user could adjust the trade-off between CPU occupation and encryption performance through MM strategy, to free CPUs according to the working requirements.
Unified Framework for Optimal Routing Choice under Guidance Information
Authors: Sun Zhi-yuan , Li Yue , Qu Wen-cong , Muhammad Tanveer
Published: August 2018

In order to satisfy the diverse demand of travel service in the context of big data, this paper puts forward a unified framework for optimal routing choice under guidance information. With consideration of the influence of big data, the scenario analysis of routing choice is implemented, and the routing choice under guidance information is discussed. The optimal routing choice problem is abstracted into the collaboration optimization model of travel route choice, departure time choice, and travel mode choice. Based on some basic assumptions, the collaboration optimization model is formulated as a variational inequality model. The method of successive averages is applied to solve the proposed model. A case study is carried out to verify the applicability and reliability of the model and algorithm.
Human Papilloma Virus Specific Immunogenicity and Dysfunction of CD8+ T Cells in Head and Neck Cancer
Authors: Krishna Sri , Ulrich Peaches , Wilson Eric , Parikh Falguni , Narang Pooja , Yang Shanshan , Read Amelia K. , Kim-Schulze Seunghee , Park Jin G. , Posner Marshall , Wilson Sayres Melissa A. , Sikora Andrew , Anderson Karen S.
Published: August 2018

Human papillomavirus subtype 16 (HPV16) is the primary cause of an increasing number of head and neck squamous cell carcinomas (HNSCC), providing strong rationale for T-cell immune therapies against HPV+ HNSCC. Here we assess immunogenicity of HPV16-specific CD8+ T cells (CTL) and characterize HPV-specific mechanisms of T-cell dysfunction. We identified 16 strong and 29 moderately immunogenic CTL-epitopes from HPV16 E2, E6, and E7 antigens restricted by 12 common HLA class I alleles. E2-specific CTL-reactivity was higher in patients with HPV+ HNSCC than in healthy controls (>3-fold; P = 0.026). Patient-derived E2, E6, and E7 peripheral CTLs exhibited heterogeneity in dysfunctional phenotypes. Immunogenomic analyses of 119 HNSCC transcriptomes revealed high T-cell infiltration and dysfunction in HPV+ HNSCC and correlation of HPV antigen expression with T-cell exhaustion gene signatures. Indoleamine 2,3-dioxygenase (IDO-1) was strongly expressed in HPV+ HNSCC versus HPV− HNSCC (P = 0.001) and correlated with E7 expression (R2 = 0.84; P = 0.033). Combination treatment with PD-1 blockade and IDO-1 inhibition overcame profound CTL-dysfunction, enhancing HPV+ HNSCC sensitivity to CTL-cytotoxicity in vitro (up to 10-fold in E7-CTLs, P = 0.011). Our findings implicate mechanisms of T-cell escape in HPV+ HNSCC, wherein high tumoral HPV-antigen load results in high expression of immune dysfunction genes on tumor cells (e.g., IDO-1), and dysfunction of HPV-specific CTLs (e.g., E7, E2-CTLs). The HPV16 CTL-epitopes identified in this study, in combination with blockade of HPV+ HNSCC-specific PD-1/IDO-1 checkpoints, may be useful for targeted immunotherapy.

Significance: This study evaluates the HPV antigen T-cell immunogenicity role of inhibitory receptors and other exhaustion markers in the cytotoxic function of HPV antigen-specific CTLs and identifies combined inhibition of PD-1/IDO-1 as a strategy to enhance CTL targeting of HPV+ HNSCC. Cancer Res; 78(21); 6159–70. ©2018 AACR.
Intrathecal Viral Vector Delivery of Trastuzumab Prevents or Inhibits Tumor Growth of Human HER2-Positive Xenografts in Mice
Authors: Rothwell William T. , Bell Peter , Richman Laura K. , Limberis Maria P. , Tretiakova Anna P. , Li Mingyao , Wilson James M.
Published: August 2018

Breast cancer brain metastases are a deadly sequela of primary breast tumors that overexpress human epidermal growth factor receptor 2 (HER2); median survival for patients with these tumors is 10 to 13 months from the time of diagnosis. Current treatments for HER2-positive breast cancer brain metastases are invasive, toxic, and largely ineffective. Here, we have developed an adeno-associated virus serotype 9 (AAV9) vector to express the anti-HER2 monoclonal antibody trastuzumab (Herceptin) in vivo. A single prophylactic intrathecal administration of AAV9.trastuzumab vector in a novel orthotopic Rag1−/− murine xenograft model of HER2-positive breast cancer brain metastases significantly increased median survival, attenuated brain tumor growth, and preserved both the HER2 antigen specificity and the natural killer cell–associated mechanism of action of trastuzumab. When administered as a tumor treatment, AAV9.trastuzumab increased median survival. Dose-escalation studies revealed that higher doses of AAV9.trastuzumab resulted in smaller tumor volumes. Our results indicate that intrathecal AAV9.trastuzumab may provide significant antitumor activity in patients with HER2-positive breast cancer brain metastases.

Significance: Intrathecal delivery of trastuzumab via adeno-associated virus has the potential to become a novel, integral part of adjuvant therapy for patients with HER2-positive breast cancer brain metastases. Cancer Res; 78(21); 6171–82. ©2018 AACR.
Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem–like Cells
Authors: Högström Jenny , Heino Sarika , Kallio Pauliina , Lähde Marianne , Leppänen Veli-Matti , Balboa Diego , Wiener Zoltán , Alitalo Kari
Published: August 2018

The homeobox transcription factor PROX1 is induced by high Wnt/β-catenin activity in intestinal adenomas and colorectal cancer, where it promotes tumor progression. Here we report that in LGR5+ colorectal cancer cells, PROX1 suppresses the Notch pathway, which is essential for cell fate in intestinal stem cells. Pharmacologic inhibition of Notch in ex vivo 3D organoid cultures from transgenic mouse intestinal adenoma models increased Prox1 expression and the number of PROX1-positive cells. Notch inhibition led to increased proliferation of the PROX1-positive colorectal cancer cells, but did not affect their ability to give rise to PROX1-negative secretory cells. Conversely, PROX1 deletion increased Notch target gene expression and NOTCH1 promoter activity, indicating reciprocal regulation between PROX1 and the Notch pathway in colorectal cancer. PROX1 interacted with the nucleosome remodeling and deacetylase (NuRD) complex to suppress the Notch pathway. Thus, our data suggests that PROX1 and Notch suppress each other and that PROX1-mediated suppression of Notch mediates its stem cell function in colorectal cancer.

Significance: These findings address the role of the PROX1 homeobox factor as a downstream effector of Wnt/β-catenin singling in colorectal cancer stem cells and show that PROX1 inhibits the Notch pathway and helps to enforce the stem cell phenotype and inhibit differentiation. Cancer Res; 78(20); 5820–32. ©2018 AACR.