bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective validation of a molecular prognostication panel for clival chordoma
Authors: Zenonos Georgios A. , Fernandez-Miranda Juan C. , Mukherjee Debraj , Chang Yue-Fang , Panayidou Klea , Snyderman Carl H. , Wang Eric W. , Seethala Raja R. , Gardner Paul A.
Published: June 2018

OBJECTIVE

There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.

METHODS

A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).

RESULTS

Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.

CONCLUSIONS

Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.
A re-evaluation of the effects of dual growing rods on apical vertebral rotation in patients with early-onset scoliosis and a minimum of two lengthening procedures: a CT-based study
Authors: Xu Liang , Qiu Yong , Chen Zhonghui , Shi Benlong , Chen Xi , Li Song , Du Changzhi , Zhu Zezhang , Sun Xu
Published: June 2018

OBJECTIVE

This study aimed to evaluate the correction results of traditional dual growing rods (DGRs) on axial rotation using CT scans and to further explore the relationships between axial and torso deformities in patients with early-onset scoliosis (EOS).

METHODS

Patients with EOS who were treated with traditional DGRs between January 2006 and December 2014 were retrospectively reviewed. Plain radiographs were used to assess the degree of coronal and sagittal deformity. The apical vertebral rotation (AVR) and rib hump (RH) were measured on CT scans at the apical vertebra. Pearson or Spearman rank correlation analyses were used to analyze the associations between spinal and torso deformities.

RESULTS

A total of 27 patients (10 boys and 17 girls, average age 6.5 ± 1.7 years) were enrolled in this study. The average number of lengthenings per patient was 5.0 ± 1.9, with a mean follow-up duration of 52.9 ± 18.2 months. The apical vertebral translation, apical vertebral body–rib ratio (AVB-R), AVR, and RH parameters were significantly decreased after the initial surgery (p < 0.05) but showed notable progression at the latest follow-up evaluation (p < 0.05). The preoperative AVR and its correction after index surgery were significantly correlated with the preoperative values as well as with the corrections of the major Cobb angle, AVB-R, and RH. During the follow-up period, significant correlations were found between the deterioration of AVR and the AVB-R and also between the deterioration of AVR and the RH from the initial surgery to the latest follow-up.

CONCLUSIONS

Significant AVR correction can be achieved by DGR techniques after the initial surgery. However, this technique weakly prevents the deterioration of AVR during the follow-up period.
Design and analysis of a voltage driving method for electro-hydraulic servo valve based on giant magnetostrictive actuator
Authors: Yang Zhaoshu , He Zhongbo , Yang Fengbiao , Rong Ce , Cui Xinhan
Published: June 2018

When large stroke of giant magnetostrictive actuator (GMA) is desired, it usually requires large number of turns in coil to generate sufficient magnetic field and therefore induce a considerable inductance in actuator. In this paper, a specific driving method is proposed for electro-hydraulic servo valve based on large inductance GMA. To begin with, a more reasonable model for the dynamics of driving coil is proposed and identified using Particle Swarm Optimization (PSO); then a specific half-SPWM driving mode is proposed taking advantages of this considerable inductance. The multi-coupled model for the overall servo valve is set up and simulated in a joint environment of Simulink and AMESim; a prototyped switching converter based on Micro Controller Unit (MCU) and Insulated-Gate Bipolar Transistor (IGBT) is developed, a series of displacement and power tests are conducted. Both simulation and test results verify the advantages of our design, compared with continuous driver the proposed method drives the coil with less power consumption and a more compact structure; compared with traditional Sinusoidal Pulse Width Modulation (SPWM) driving mode, this method generates a smoother wave using less switch number and less switching losses.
Effects of Height and Plan Geometry on the Costs of Tunnel Form Residential Buildings
Authors: İlerisoy Zeynep Yeşim , Tuna Mehmet Emin
Published: June 2018

Tunnel form systems, which are industrialised construction systems developed in the last century, are widely used in reinforced concrete projects. Accurate determination of the costs of the building properties in the design phases of construction with the tunnel form system can lead to lower construction costs. The purpose of this study is to examine the cost variations resulting from changes in geometrical characteristics of buildings in the architectural design phase. The research was carried out on residential projects, which have the biggest share in the construction sector. Six housing projects with different plan geometries were designed, and these projects were examined for nine different numbers of floors. The study aims to reveal the extent to which both the plan shape and the number of floors influence the building costs. During the design phase, recommendations are given for reducing the building costs and finding the optimal form. It has been shown that tunnel form projects are not cost-effective in low-rise buildings and after a certain height. Furthermore, when different geometries are examined, the most economical cost is obtained in square form, and the cost increases as the two dimensions in plan plane move away from each other. As a result, the data obtained from this study will provide a better assessment of the relationship between building properties and unit cost in buildings constructed with tunnel form systems.
Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic Strategy for Breast Cancer
Authors: Mostafa Ahmed A. , Meyers Daniel E. , Thirukkumaran Chandini M. , Liu Peter J. , Gratton Kathy , Spurrell Jason , Shi Qiao , Thakur Satbir , Morris Don G.
Published: June 2018

As the current efficacy of oncolytic viruses (OVs) as monotherapy is limited, exploration of OVs as part of a broader immunotherapeutic treatment strategy for cancer is necessary. Here, we investigated the ability for immune checkpoint blockade to enhance the efficacy of oncolytic reovirus (RV) for the treatment of breast cancer (BrCa). In vitro, oncolysis and cytokine production were assessed in human and murine BrCa cell lines following RV exposure. Furthermore, RV-induced upregulation of tumor cell PD-L1 was evaluated. In vivo, the immunocompetent, syngeneic EMT6 murine model of BrCa was employed to determine therapeutic and tumor-specific immune responses following treatment with RV, anti-PD-1 antibodies or in combination. RV-mediated oncolysis and cytokine production were observed following BrCa cell infection and RV upregulated tumor cell expression of PD-L1. In vivo, RV monotherapy significantly reduced disease burden and enhanced survival in treated mice, and was further enhanced by PD-1 blockade. RV therapy increased the number of intratumoral regulatory T cells, which was reversed by the addition of PD-1 blockade. Finally, dual treatment led to the generation of a systemic adaptive anti-tumor immune response evidenced by an increase in tumor-specific IFN-γ producing CD8+ T cells, and immunity from tumor re-challenge. The combination of PD-1 blockade and RV appears to be an efficacious immunotherapeutic strategy for the treatment of BrCa, and warrants further investigation in early-phase clinical trials.
Forecasting the Long-Term Wind Data via Measure-Correlate-Predict (MCP) Methods
Authors: Ali Sajid , Lee Sang-Moon , Jang Choon-Man
Published: June 2018

The current study aims to forecast and analyze wind data such as wind speed at a test site called “Urumsill” on Deokjeok Island, South Korea. The measured wind data available at the aforementioned test site are only for two years (2015 and 2016), making it impossible to analyze the long-term wind characteristics. In order to overcome this problem, two measure-correlate-predict (MCP) techniques were adopted using long-term wind data (2000–2016), measured by a meteorological mast (met-mast) installed at a distance of 3 km from the test site. The wind data measured at the test site in 2016 were selected as training data to build the MCP models, whereas wind data of 2015 were used to test the accuracy of MCP models (test data). The wind data at both sites were measured at a height of 10 m and showed a good agreement for the year 2016 (training period). Using the comparison results of the year 2016, wind speed predictions were made for the rest of the years (2000–2016) at the test site. The forecasted values of wind speed had maximum relative error in the range of ±0.8 m/s for the test year of 2105. The predicted wind data values were further analyzed by estimating the mean wind speed, the Weibull shape, and the scale parameters, on a seasonal and an annual basis, in order to understand the wind behavior in the region. The accuracy and presence of possible errors in the forecasted wind data are discussed and presented.
Decision Variants for the Automatic Determination of Optimal Feature Subset in RF-RFE
Authors: Chen Qi , Meng Zhaopeng , Liu Xinyi , Jin Qianguo , Su Ran
Published: June 2018

Feature selection, which identifies a set of most informative features from the original feature space, has been widely used to simplify the predictor. Recursive feature elimination (RFE), as one of the most popular feature selection approaches, is effective in data dimension reduction and efficiency increase. A ranking of features, as well as candidate subsets with the corresponding accuracy, is produced through RFE. The subset with highest accuracy (HA) or a preset number of features (PreNum) are often used as the final subset. However, this may lead to a large number of features being selected, or if there is no prior knowledge about this preset number, it is often ambiguous and subjective regarding final subset selection. A proper decision variant is in high demand to automatically determine the optimal subset. In this study, we conduct pioneering work to explore the decision variant after obtaining a list of candidate subsets from RFE. We provide a detailed analysis and comparison of several decision variants to automatically select the optimal feature subset. Random forest (RF)-recursive feature elimination (RF-RFE) algorithm and a voting strategy are introduced. We validated the variants on two totally different molecular biology datasets, one for a toxicogenomic study and the other one for protein sequence analysis. The study provides an automated way to determine the optimal feature subset when using RF-RFE.
Traditional Chinese Medical Care and Incidence of Stroke in Elderly Patients Treated with Antidiabetic Medications
Authors: Chiao Yun-Wen , Chen Yu-Jen , Kuo Yu-Hsien , Lu Chung-Yen
Published: June 2018

Objectives: Experimental research has shown that herbal and traditional Chinese medicines (TCM) may serve as complements to Western medicine treatments in the control of blood glucose and cardiovascular complications, but population-based studies are limited. We investigated the association between TCM use and subsequent risk of stroke in older patients with diabetes. Study design: The database used in this cohort study contained longitudinal medical claims for one million subjects randomly selected among beneficiaries of a universal health care program in Taiwan. We identified a cohort of patients with diabetes aged 65 years and older who initiated anti-diabetic medications from 2000 to 2012. Patients who had at least two TCM outpatient visits after their initiation of anti-diabetic medications were considered TCM users. Main outcome measures: The incidence of stroke was measured until 2013. Cox regression models with TCM use as a time-dependent variable were used to calculate the adjusted hazard ratios (HRs) comparing TCM use with no use. Results: Over the 13-year period, 17,015 patients were identified; 4912 (28.9%) of them were TCM users. The incidence of stroke during the follow-up (per 1000 person-years) was 22.8 in TCM users and 25.7 in non-users. TCM users had an adjusted HR of 0.93 for the incidence of ischemic stroke (95% confidence interval [CI] 0.83, 1.04) and of 0.89 for developing hemorrhagic stroke (95% CI 0.66, 1.19), compared with non-users. Conclusions: In this study, in older patients receiving Western medicine treatments for diabetes, TCM use was not associated with an increased risk of developing ischemic stroke and hemorrhagic stroke.
Transcriptome Analysis Provides Insight into the Molecular Mechanisms Underlying gametophyte factor 2-Mediated Cross-Incompatibility in Maize
Authors: Wang Man , Chen Zhibin , Zhang Huairen , Chen Huabang , Gao Xiquan
Published: June 2018

In maize (Zea mays L.), unilateral cross-incompatibility (UCI) is controlled by Gametophyte factors (Ga), including Ga1, Ga2, and Tcb1; however, the molecular mechanisms underpinning this process remain unexplored. Here, we report the pollination phenotype of an inbred line, 511L, which carries a near-dominant Ga2-S allele. We performed a high-throughput RNA sequencing (RNA-Seq) analysis of the compatible and incompatible crosses between 511L and B73, to identify the transcriptomic differences associated with Ga2-mediated UCI. An in vivo kinetics analysis revealed that the growth of non-self pollen tubes was blocked at the early stages after pollination in 511L, maintaining the UCI barrier in Ga2. In total, 25,759 genes were expressed, of which, 2063 differentially expressed genes (DEGs) were induced by pollination (G_GG, G_GB, B_BB, B_BG). A gene ontology (GO) enrichment analysis revealed that these genes were specifically enriched in functions involved in cell wall strength and pectic product modification. Moreover, 1839, 4382, and 5041 genes were detected to differentially express under same pollination treatments, including B_G, BG_GG, and BB_GB, respectively. A total of 1467 DEGs were constitutively expressed between the two inbred lines following pollination treatments, which were enriched in metabolic processes, flavonoid biosynthesis, cysteine biosynthesis, and vacuole functions. Furthermore, we confirmed 14 DEGs related to cell wall modification and stress by qRT-PCR, which might be involved in Ga2-S-mediated UCI. Our results provide a comprehensive foundation for the molecular mechanisms involved in silks of UCI mediated by Ga2-S.
Human Papilloma Virus and Autophagy
Authors: Mattoscio Domenico , Medda Alessandro , Chiocca Susanna
Published: June 2018

Human papilloma viruses (HPVs) are a group of double-stranded DNA viruses known to be the primary cause of cervical cancer. In addition, evidence has now established their role in non-melanoma skin cancers, head and neck cancer (HNC), and the development of other anogenital malignancies. The prevalence of HPV-related HNC, in particular oropharyngeal cancers, is rapidly increasing, foreseeing that HPV-positive oropharyngeal cancers will outnumber uterine cervical cancers in the next 15–20 years. Therefore, despite the successful advent of vaccines originally licensed for cervical cancer prevention, HPV burden is still very high, and a better understanding of HPV biology is urgently needed. Autophagy is the physiological cellular route that accounts for removal, degradation, and recycling of damaged organelles, proteins, and lipids in lysosomal vacuoles. In addition to this scavenger function, autophagy plays a fundamental role during viral infections and cancers and is, therefore, frequently exploited by viruses to their own benefit. Recently, a link between HPV and autophagy has clearly emerged, leading to the conceivable development of novel anti-viral strategies aimed at restraining HPV infectivity. Here, recent findings on how oncogenic HPV16 usurp autophagy are described, highlighting similarities and differences with mechanisms adopted by other oncoviruses.
Endocrine Disruption at the Androgen Receptor: Employing Molecular Dynamics and Docking for Improved Virtual Screening and Toxicity Prediction
Authors: Wahl Joel , Smieško Martin
Published: June 2018

The androgen receptor (AR) is a key target for the development of drugs targeting hormone-dependent prostate cancer, but has also an important role in endocrine disruption. Reliable prediction of the binding of ligands towards the AR is therefore of great relevance. Molecular docking is a powerful computational method for exploring small-ligand binding to proteins. It can be applied for virtual screening experiments but also for predicting molecular initiating events in toxicology. However, in case of AR, there is no antagonist-bound crystal structure yet available. Our study demonstrates that molecular docking approaches are not able to satisfactorily screen for AR antagonists because of this reason. Therefore, we applied Molecular Dynamics simulations to generate antagonist AR structures and showed that this leads to a vast improvement for the docking of AR antagonists. We benchmarked the ability of these antagonist AR structures discriminate between AR antagonists and decoys using an ensemble docking approach and obtained promising results with good enrichment. However, distinguishing AR antagonists from agonists with high confidence is not possible with the current approach alone.
Peculiarities in the Material Design of Buckling Resistance for Tensioned Laminated Composite Panels with Elliptical Cut-Outs
Authors: Muc Aleksander
Published: June 2018

The results of analytical and numerical studies of the buckling behavior of laminated multilayered tensioned sheets with circular and elliptical openings are presented. The analysis shows the significant influence of stress concentration effects on buckling modes and loads, particularly taking into consideration variations in the E1/E2 and E1/G12 ratios. The results of finite element (FE) computations prove that the buckling mode cannot be described by a single buckle localized at the apex of the hole. The optimal design of such structures seems to be much more complicated than classical buckling problems of compressed laminated panels without holes. However, the obtained results indicate that the optimal laminate configurations occur at the boundaries of the feasible regions of the introduced design space. Both continuous and discrete fibre orientations are considered. For continuous fibre orientations, the optimal stacking sequence corresponds to angle-ply symmetric laminates.
Redox Activity of Sodium Vanadium Oxides towards Oxidation in Na Ion Batteries
Authors: Adamczyk Evan , Gnanavel Muthaiyan , Pralong Valerie
Published: June 2018

The search for new materials that could be used as electrode material for Na-ion batteries is one of the most challenging issues of today. Many transition metal oxide families as well as transition metal polyanionic frameworks have been proposed over the last five years. In this work, we report the sodium extraction from Na2V3O7, which is a tunnel type structure built of [V3O7]2−∞ nanotubes held by sodium ions. We report a reversible charge capacity of 80 mAh/g at 2.8 V vs. Na+/Na due to the V5+/V4+ redox activity. No oxygen redox activity has been observed for this material nor for the vanadium (5+) oxide Na4V2O7.
The Holo-Transcriptome of the Zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa): A Plentiful Source of Enzymes for Potential Application in Green Chemistry, Industrial and Pharmaceutical Biotechnology
Authors: R. L. Morlighem Jean-Étienne , Huang Chen , Liao Qiwen , Braga Gomes Paula , Daniel Pérez Carlos , De Brandão Prieto-da-Silva Álvaro Rossan , Ming-Yuen Lee Simon , Rádis-Baptista Gandhi
Published: June 2018

Marine invertebrates, such as sponges, tunicates and cnidarians (zoantharians and scleractinian corals), form functional assemblages, known as holobionts, with numerous microbes. This type of species-specific symbiotic association can be a repository of myriad valuable low molecular weight organic compounds, bioactive peptides and enzymes. The zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa) is one such example of a marine holobiont that inhabits the coastal reefs of the tropical Atlantic coast and is an interesting source of secondary metabolites and biologically active polypeptides. In the present study, we analyzed the entire holo-transcriptome of P. variabilis, looking for enzyme precursors expressed in the zoantharian-microbiota assemblage that are potentially useful as industrial biocatalysts and biopharmaceuticals. In addition to hundreds of predicted enzymes that fit into the classes of hydrolases, oxidoreductases and transferases that were found, novel enzyme precursors with multiple activities in single structures and enzymes with incomplete Enzyme Commission numbers were revealed. Our results indicated the predictive expression of thirteen multifunctional enzymes and 694 enzyme sequences with partially characterized activities, distributed in 23 sub-subclasses. These predicted enzyme structures and activities can prospectively be harnessed for applications in diverse areas of industrial and pharmaceutical biotechnology.
Pseudomonas aeruginosa bacteremia: Associations with a source of infection and antibiotic resistance
Authors: Dambrauskienė Asta , Adukauskienė Dalia , Jeroch Jolanta , Vitkauskienė Astra
Published: June 2018

Aim of the study. To determine the associations between the source of infection and antibiotic resistance in patients with Pseudomonas aeruginosa bacteremia. Material and methods. A retrospective analysis of 50 patients with Pseudomonas aeruginosa bacteremia was carried out. If sepsis was suspected, blood culture was incubated in an automatic system BACTEC 9240. Then bacteria were identified, and their antibiotic resistance was estimated by disc diffusion method. If Pseudomonas aeruginosa strains were resistant to three or more antibiotics, they were considered as multidrug-resistant.Results. The origin of bacteremia was confirmed in 33 (66%) patients. Lower respiratory tract was the predominant source of Pseudomonas aeruginosa bacteremia (81.8%, n=27) as compared with infection of wound (39.4%, n=13), urinary tract (15.2%, n=5), and drain or cerebrospinal fluid (9.1%, n=3) (P<0.05). Eighteen percent (n=9) of strains, which caused bacteremia, were resistant to ceftazidime; 38% (n=19), to piperacillin; 22% (n=11), to imipenem; 26% (n=13), to meropenem; 24% (n=12), to ciprofloxacin; 40% (n=20), to gentamicin; and only 8% (n=4), to amikacin. Multidrug-resistant Pseudomonas aeruginosa strains were more frequently isolated if a source of infection was wound comparing to a source of other localization (61.5%, n=8 and 20.0%, n=4, respectively; P<0.05). Resistance of Pseudomonas aeruginosa strains to imipenem was associated with resistance to ciprofloxacin (13.2%, n=5 and 50.0%, n=6, retrospectively; P<0.05), but resistance to meropenem – both to ciprofloxacin and amikacin. Conclusions. The predominant source of Pseudomonas aeruginosa bacteremia was lower respiratory tract, and multidrug-resistant strains caused bacteremia more frequently if a source infection was wound. Pseudomonas aeruginosa resistance to carbapenems was associated with resistance to ciprofloxacin and resistance to meropenem – also to amikacin. Resistance of strains to ceftazidime and piperacillin was associated with resistance to gentamicin.
Motor control theories and their applications
Authors: Latash Mark , Levin Mindy , Scholz John , Schöner Gregor
Published: June 2018

We describe several infl uential hypotheses in the field of motor control including the equilibrium-point (referent confi guration) hypothesis, the uncontrolled manifold hypothesis, and the idea of synergies based on the principle of motor abundance. The equilibrium-point hypothesis is based on the idea of control with thresholds for activation of neuronal pools; it provides a framework for analysis of both voluntary and involuntary movements. In particular, control of a single muscle can be adequately described with changes in the threshold of motor unit recruitment during slow muscle stretch (threshold of the tonic stretch reflex). Unlike the ideas of internal models, the equilibrium-point hypothesis does not assume neural computations of mechanical variables. The uncontrolled manifold hypothesis is based on the dynamic system approach to movements; it offers a toolbox to analyze synergic changes within redundant sets of elements related to stabilization of potentially important performance variables. The referent confi guration hypothesis and the principle of abundance can be naturally combined into a single coherent scheme of control of multi-element systems. A body of experimental data on healthy persons and patients with movement disorders are reviewed in support of the mentioned hypotheses. In particular, movement disorders associated with spasticity are considered as consequences of an impaired ability to shift threshold of the tonic stretch reflex within the whole normal range. Technical details and applications of the mentioned hypo theses to studies of motor learning are described. We view the mentioned hypotheses as the most promising ones in the field of motor control, based on a solid physical and neurophysiological foundation.
A Facile Interfacial Self-Assembly of Crystalline Colloidal Monolayers by Tension Gradient
Authors: Feng Dong , Weng Ding , Wang Jiadao
Published: June 2018

Many self-assembly approaches of colloidal monolayers have flourished but with some shortages, such as complexity, time-consumption, parameter sensitivity, and high-cost. This paper presents a facile, rapid, well-controlled, and low-cost method to prepare monolayers by directly adding silica particle suspensions containing water and ethanol to different liquids. A detailed analysis of the self-assembly process was conducted. The particles dove into water firstly, then moved up under the effect of the buoyancy and the tension gradient. The tension gradient induced the Marangoni convection and the relative motion between the water and the particles. At last, the particles were adsorbed at the air-water interface to minimize the free energy. The quality of the monolayers depended on the addition of sodium dodecyl sulfonate or ethanol in the water subphase. An interfacial polymerization of ethyl 2-cyanoacrylate was used to determine the contact angles of the particles at different subphase surfaces. The value of the detachment energy was positively associated with the contact angle and the surface tension. When the detachment energy decreased to a certain value, some particles detached from the surface, leading to the formation of a quasi-double layer. We also observed that the content of ethanol in suspensions influenced the arrangement of particles.
Multiscale Analysis of Size Effect of Surface Pit Defect in Nanoindentation
Authors: Zhang Zhongli , Ni Yushan , Zhang Jinming , Wang Can , Ren Xuedi
Published: June 2018

The nanoindentation on a pit surface has been simulated using the quasicontinuum method in order to investigate the size effect of surface pit defect on the yield load of thin film. Various widths and heights of surface pit defect have been taken into account. The size coefficient has been defined as an index to express the influence of the width or height of surface pit defect. The results show that as the size coefficient of width (of height) increases, at first the yield load of thin film decreases extremely slowly, until the size coefficient of width equals approximately one unit (half unit), at which point the yield load experiences an obvious drop. When the size coefficient of width (of height) reaches approximately two units (one unit), the yield load is almost the same as that of the nanoindentation on a stepped surface. In addition, the height of surface pit defect has more influence than the width on the yield load of thin film.
Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy
Authors: Zhang Juan , Tavares de Sousa Júnior Wellington , Mello da Silva Victor Carlos , Rodrigues Mosar Correa , Vasconcelos Morais José Athayde , Song Jia-Li , Cheng Zhi-Qiang , Longo João Paulo Figueiró , Bentes Azevedo Ricardo , Jiang Cheng-Shi , Alexandre Muehlmann Luís , Zhang Hua
Published: June 2018

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.
Phosphoproteomics of Retinoblastoma: A Pilot Study Identifies Aberrant Kinases
Authors: Selvan Lakshmi Dhevi Nagarajha , Danda Ravikanth , Madugundu Anil K. , Puttamallesh Vinuth N. , Sathe Gajanan J. , Krishnan Uma Maheswari , Khetan Vikas , Rishi Pukhraj , Prasad Thottethodi Subrahmanya Keshava , Pandey Akhilesh , Krishnakumar Subramanian , Gowda Harsha , Elchuri Sailaja V.
Published: June 2018

Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phosphoproteomics of retinoblastoma (RB) was carried out to identify signalling events associated with this cancer. Over 350 proteins showed differential phosphorylation in RB compared to control retina. Our study identified stress response proteins to be hyperphosphorylated in RB which included H2A histone family member X (H2AFX) and sirtuin 1. In particular, Ser140 of H2AFX also known as gamma-H2AX was found to be hyperphosphorylated in retinoblastoma, which indicated the activation of DNA damage response pathways. We also observed the activation of anti-apoptosis in retinoblastoma compared to control. These observations showed the activation of survival pathways in retinoblastoma. The identification of hyperphosphorylated protein kinases including Bromodomain containing 4 (BRD4), Lysine deficient protein kinase 1 (WNK1), and Cyclin-dependent kinase 1 (CDK1) in RB opens new avenues for the treatment of RB. These kinases can be considered as probable therapeutic targets for RB, as small-molecule inhibitors for some of these kinases are already in clinical trials for the treatment other cancers.
The Possible Reduction Mechanism of Volatile Sulfur Compounds during Durian Wine Fermentation Verified in Modified Buffers
Authors: Lu Yuyun , Fong Alicia Sarah Yoke Ling , Chua Jian-Yong , Huang Dejian , Lee Pin-Rou , Liu Shao-Quan
Published: June 2018

Durian fruit is rich in volatile sulfur compounds (VSCs), especially thiols and disulfides, which contribute to its onion-like odor. After fermentation, these VSCs were reduced to trace or undetectable levels in durian wine. The possible reduction mechanism of these VSCs (especially diethyl disulfide and ethanethiol) was investigated in a modified buffer in the presence of sulfite at different pH. An interconversion between diethyl disulfide and ethanethiol was found to be dependent on the pH: the higher the pH, the higher production of ethanethiol. It is suggested that, during durian wine fermentation, disulfides endogenous to durian pulp might be firstly converted into their corresponding thiols in the presence of reductant sulfite formed by yeast. The produced thiols as well as the thiols endogenous to the durian pulp were then removed by the mannoproteins of yeast lees.
Phosphorus Pentachloride Promoted gem-Dichlorination of 2′- and 3′-Deoxynucleosides
Authors: Da Paixao Soares Fabio , Groaz Elisabetta , Herdewijn Piet
Published: June 2018

Halogen substitution at various positions of canonical nucleosides has generated a number of bioactive structural variants. Herein, the synthesis of two unique series of sugar modified nucleosides bearing a gem-dichloro group is presented. The synthetic plan entails the controlled addition of phosphorus pentachloride to suitably protected 2′- or 3′-ketodeoxynucleoside intermediates as the key step, facilitating the rapid construction of such functionalized molecules. Under the same reaction conditions, the highest chemoselectivity was observed for the formation of 2′,2′-dichloro-2′,3′-dideoxynucleosides, while a competing 2′,3′-elimination process occurred in the case of the 3′,3′-dichloro counterparts.
Density Functional Theory Analysis of Deltamethrin and Its Determination in Strawberry by Surface Enhanced Raman Spectroscopy
Authors: Dong Tao , Lin Lei , He Yong , Nie Pengcheng , Qu Fangfang , Xiao Shupei
Published: June 2018

Deltamethrin is widely used in pest prevention and control such as red spiders, aphids, and grubs in strawberry. It is important to accurately monitor whether the deltamethrin residue in strawberry exceeds the standard. In this paper, density functional theory (DFT) was used to theoretically analyze the molecular structure of deltamethrin, gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) were used to enhance the surface enhanced Raman spectroscopy (SERS) detection signal. As a result, the theoretical Raman peaks of deltamethrin calculated by DFT were basically similar to the measured results, and the enhancing effects based on AuNPs was better than that of AgNPs. Moreover, 554, 736, 776, 964, 1000, 1166, 1206, 1593, 1613, and 1735 cm−1 could be determined as deltamethrin characteristic peaks, among which only three Raman peaks (736, 1000, and 1166 cm−1) could be used as the deltamethrin characteristic peaks in strawberry when the detection limit reached 0.1 mg/L. In addition, the 500–1800 cm−1 SERS of deltamethrin were analyzed by the partial least squares (PLS) and backward interval partial least squares (BIPLS). The prediction accuracy of deltamethrin in strawberry (Rp2 = 0.93, RMSEp = 4.66 mg/L, RPD = 3.59) was the highest when the original spectra were pretreated by multiplicative scatter correction (MSC) and then modeled by BIPLS. In conclusion, the deltamethrin in strawberry could be qualitatively analyzed and quantitatively determined by SERS based on AuNPs enhancement, which provides a new detection scheme for deltamethrin residue determination in strawberry.
Pyridine-Ureas as Potential Anticancer Agents: Synthesis and In Vitro Biological Evaluation
Authors: El-Naggar Mohamed , Almahli Hadia , Ibrahim Hany S. , Eldehna Wagdy M. , Abdel-Aziz Hatem A.
Published: June 2018

In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a–n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC50 = 0.22 and 1.88 µM after 48 h treatment; 0.11 and 0.80 µM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC50 = 1.93 µM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l–n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12–78%, GI for 8e; 15–91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC50 values 5.0 ± 1.91 and 3.93 ± 0.73 µM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.
Detection of Protein Complexes Based on Penalized Matrix Decomposition in a Sparse Protein–Protein Interaction Network
Authors: Cao Buwen , Deng Shuguang , Qin Hua , Ding Pingjian , Chen Shaopeng , Li Guanghui
Published: June 2018

High-throughput technology has generated large-scale protein interaction data, which is crucial in our understanding of biological organisms. Many complex identification algorithms have been developed to determine protein complexes. However, these methods are only suitable for dense protein interaction networks, because their capabilities decrease rapidly when applied to sparse protein–protein interaction (PPI) networks. In this study, based on penalized matrix decomposition (PMD), a novel method of penalized matrix decomposition for the identification of protein complexes (i.e., PMDpc) was developed to detect protein complexes in the human protein interaction network. This method mainly consists of three steps. First, the adjacent matrix of the protein interaction network is normalized. Second, the normalized matrix is decomposed into three factor matrices. The PMDpc method can detect protein complexes in sparse PPI networks by imposing appropriate constraints on factor matrices. Finally, the results of our method are compared with those of other methods in human PPI network. Experimental results show that our method can not only outperform classical algorithms, such as CFinder, ClusterONE, RRW, HC-PIN, and PCE-FR, but can also achieve an ideal overall performance in terms of a composite score consisting of F-measure, accuracy (ACC), and the maximum matching ratio (MMR).
Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis
Authors: Zimmermann Tomas , Christensen Søren Brøgger , Franzyk Henrik
Published: June 2018

Since cells in solid tumors divide less rapidly than cells in the bone marrow or cells of the immune system, mitotic inhibitors often cause severe side effects when used for treatment of diseases like prostate cancer and breast cancer. One approach to overcome this problem involves attempts at developing drugs based on general cytotoxins, like calicheamicin and thapsigargin, which kill cells at all phases of the cell cycle. However, such toxins can only be used when efficient targeting to the malignant tissue is possible. In the case of thapsigargin, selectivity for tumor-associated cells is achieved by conjugating the drug to a peptide that is only cleaved in the vicinity of tumors to release the cytotoxic drug or an analog with retained activity. Solid-phase synthesis protocols were developed for preparation of three already validated prodrugs of thapsigargin: one prodrug cleavable by human kallikrein 2, one prodrug cleavable by prostate-specific antigen, and one prodrug cleavable by prostate-specific membrane antigen.
The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins
Authors: Bird Julia K. , Calder Philip C. , Eggersdorfer Manfred
Published: June 2018

Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.
A Novel Approach for the Short-Term Forecast of the Effective Cloud Albedo
Authors: Urbich Isabel , Bendix Jörg , Müller Richard
Published: June 2018

The increasing use of renewable energies as a source of electricity has led to a fundamental transition of the power supply system. The integration of fluctuating weather-dependent energy sources into the grid already has a major impact on its load flows. As a result, the interest in forecasting wind and solar radiation with a sufficient accuracy over short time periods (<4 h) has grown. In this study, the short-term forecast of the effective cloud albedo based on optical flow estimation methods is investigated. The optical flow method utilized here is TV-L1 from the open source library OpenCV. This method uses a multi-scale approach to capture cloud motions on various spatial scales. After the clouds are displaced, the solar surface radiation will be calculated with SPECMAGIC NOW, which computes the global irradiation spectrally resolved from satellite imagery. Due to the high temporal and spatial resolution of satellite measurements, the effective cloud albedo and thus solar radiation can be forecasted from 5 min up to 4 h with a resolution of 0.05°. The validation results of this method are very promising, and the RMSE of the 30-min, 60-min, 90-min and 120-min forecast equals 10.47%, 14.28%, 16.87% and 18.83%, respectively. The paper gives a brief description of the method for the short-term forecast of the effective cloud albedo. Subsequently, evaluation results will be presented and discussed.
A Direct Position-Determination Approach for Multiple Sources Based on Neural Network Computation
Authors: Chen Xin , Wang Ding , Yin Jiexin , Wu Ying
Published: June 2018

The most widely used localization technology is the two-step method that localizes transmitters by measuring one or more specified positioning parameters. Direct position determination (DPD) is a promising technique that directly localizes transmitters from sensor outputs and can offer superior localization performance. However, existing DPD algorithms such as maximum likelihood (ML)-based and multiple signal classification (MUSIC)-based estimations are computationally expensive, making it difficult to satisfy real-time demands. To solve this problem, we propose the use of a modular neural network for multiple-source DPD. In this method, the area of interest is divided into multiple sub-areas. Multilayer perceptron (MLP) neural networks are employed to detect the presence of a source in a sub-area and filter sources in other sub-areas, and radial basis function (RBF) neural networks are utilized for position estimation. Simulation results show that a number of appropriately trained neural networks can be successfully used for DPD. The performance of the proposed MLP-MLP-RBF method is comparable to the performance of the conventional MUSIC-based DPD algorithm for various signal-to-noise ratios and signal power ratios. Furthermore, the MLP-MLP-RBF network is less computationally intensive than the classical DPD algorithm and is therefore an attractive choice for real-time applications.
Energy-Aware Computation Offloading of IoT Sensors in Cloudlet-Based Mobile Edge Computing
Authors: Ma Xiao , Lin Chuang , Zhang Han , Liu Jianwei
Published: June 2018

Mobile edge computing is proposed as a promising computing paradigm to relieve the excessive burden of data centers and mobile networks, which is induced by the rapid growth of Internet of Things (IoT). This work introduces the cloud-assisted multi-cloudlet framework to provision scalable services in cloudlet-based mobile edge computing. Due to the constrained computation resources of cloudlets and limited communication resources of wireless access points (APs), IoT sensors with identical computation offloading decisions interact with each other. To optimize the processing delay and energy consumption of computation tasks, theoretic analysis of the computation offloading decision problem of IoT sensors is presented in this paper. In more detail, the computation offloading decision problem of IoT sensors is formulated as a computation offloading game and the condition of Nash equilibrium is derived by introducing the tool of a potential game. By exploiting the finite improvement property of the game, the Computation Offloading Decision (COD) algorithm is designed to provide decentralized computation offloading strategies for IoT sensors. Simulation results demonstrate that the COD algorithm can significantly reduce the system cost compared with the random-selection algorithm and the cloud-first algorithm. Furthermore, the COD algorithm can scale well with increasing IoT sensors.
Landscape Connectivity as a Tool in Green Space Evaluation and Optimization of the Haidan District, Beijing
Authors: Guo Shiyi , Saito Kaoru , Yin Weida , Su Chang
Published: June 2018

The demand for urban construction has placed growing pressure on biodiversity conservation. In China, landscape fragmentation caused by rapid urbanization has resulted in an immense amount of damage to the ecological system. Taking the Haidian District of Beijing as the study area, this study distinguishes the vital patches and corridors for landscape connectivity maintenance through morphological spatial pattern analysis (MSPA), the probability of connectivity (PC), and the least-cost path analysis. Although we adopted and combined these methods from the existing research about landscape modeling, we went deeper into two parameters: the resistance value and the distance threshold. In order to get a species-specific result, we selected two focal species: the ring-necked pheasant (Phasianus colchius) and the raccoon dog (Nyctereutes procyonoides), whose biological characteristics and habitat types are assumed to represent most of the habitats in Beijing. The result shows the different habitats and corridors for two species. Then, the results of two simulated scenarios are overlaid to obtain the final landscape pattern. Based on this case study, we propose a paradigm of ecological network identification of multiple species, which may contribute to landscape modeling and green space planning.