bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Optical Properties, and DNA Interaction of New Diquats Based on Triazolopyridines and Triazoloquinolines
Authors: Llabres‐Campaner Pedro J. , Guijarro Lluís , Giarratano Claudia , Ballesteros‐Garrido Rafael , Zaragozá Ramón J. , Aurell M. José , García‐España Enrique , Ballesteros Rafael , Abarca Belén
Published: August 2017

New diquat derivatives based on [1,2,3]triazolo[1,5‐a]pyridine and [1,2,3]triazolo[1,5‐a]quinoline have been synthesized in excellent yields. To evaluate the effect of the alkyl bridge length, ethane and propane dibromo alkane substrates were used for their synthesis. Theoretical calculations predicted a very small energetic barrier between the two possible enantiomers P (Ra) and M (Sa), which makes them very difficult to resolve. Thermal denaturation studies, UV/Visible spectroscopy, and fluorescence titrations with ct‐DNA evidenced the intercalation of the quinoline derivatives in DNA.
Octadentate Picolinic Acid‐Based Bispidine Ligand for Radiometal Ions
Authors: Comba Peter , Jermilova Una , Orvig Chris , Patrick Brian O. , Ramogida Caterina F. , Rück Katharina , Schneider Christina , Starke Miriam
Published: August 2017

The synthesis of the octadentate bispidine ligand bearing two picolinic acid pendant arms (H2bispa2), and its coordination chemistry with radionuclides relevant for nuclear medicine, namely indium(III) (111In), lutetium(III) (177Lu), and lanthanum(III) (as surrogate for 225Ac), are reported. The non‐radioactive metal complexes of the N6O2‐type bispa ligand were characterized by 1H and 13C NMR spectroscopy, elemental analysis, mass spectrometry and single‐crystal X‐ray analysis. Experimental structural data, computational analysis, complex stabilities determined by potentiometric titration, and “radiostabilities” determined by competition studies in the presence of human serum reveal complex stabilities of H2bispa2 comparable to those of the macrocyclic “gold standard” DOTA. After an incubation time of 1 day, 86 and 87 % of [177Lu(bispa2)]+ and [177Lu(DOTA)]−, respectively, remain intact. Importantly, unlike DOTA, H2bispa2 is radiolabeled quantitatively with 111InIII and 225AcIII under ambient conditions, which is an essential aspect when working with heat‐sensitive antibodies as targeting vectors. In the case of 111InIII, room temperature radiolabeling of H2bispa2 yields molar activities as high as 70 MBq nmol−1 within 10 minutes. These are promising results for radiopharmaceutical applications of H2bispa2.
Rhenium‐Loaded TiO2: A Highly Versatile and Chemoselective Catalyst for the Hydrogenation of Carboxylic Acid Derivatives and the N‐Methylation of Amines Using H2 and CO2
Authors: Toyao Takashi , Siddiki S. M. A. H. , Morita Yoshitsugu , Kamachi Takashi , Touchy Abeda S. , Onodera Wataru , Kon Kenichi , Furukawa Shinya , Ariga Hiroko , Asakura Kiyotaka , Yoshizawa Kazunari , Shimizu Ken‐ichi
Published: August 2017

Herein, we report a heterogeneous TiO2‐supported Re catalyst (Re/TiO2) that promotes various selective hydrogenation reactions, which includes the hydrogenation of esters to alcohols, the hydrogenation of amides to amines, and the N‐methylation of amines, by using H2 and CO2. Initially, Re/TiO2 was evaluated in the context of the selective hydrogenation of 3‐phenylpropionic acid methyl ester to afford 3‐phenylpropanol (p
=5 MPa, T=180 °C), which revealed a superior performance over other catalysts that we tested in this study. In contrast to other typical heterogeneous catalysts, hydrogenation reactions with Re/TiO2 did not produce dearomatized byproducts. DFT studies suggested that the high selectivity for the formation of alcohols in favor of the hydrogenation of aromatic rings is ascribed to the higher affinity of Re towards the COOCH3 group than to the benzene ring. Moreover, Re/TiO2 showed a wide substrate scope for the hydrogenation reaction (19 examples). Subsequently, this Re/TiO2 catalyst was applied to the hydrogenation of amides, the N‐methylation of amines, and the N‐alkylation of amines with carboxylic acids or esters.
Prediction of Reduction Potentials of Copper Proteins with Continuum Electrostatics and Density Functional Theory
Authors: Fowler Nicholas J. , Blanford Christopher F. , Warwicker Jim , de Visser Sam P.
Published: August 2017

Blue copper proteins, such as azurin, show dramatic changes in Cu2+/Cu+ reduction potential upon mutation over the full physiological range. Hence, they have important functions in electron transfer and oxidation chemistry and have applications in industrial biotechnology. The details of what determines these reduction potential changes upon mutation are still unclear. Moreover, it has been difficult to model and predict the reduction potential of azurin mutants and currently no unique procedure or workflow pattern exists. Furthermore, high‐level computational methods can be accurate but are too time consuming for practical use. In this work, a novel approach for calculating reduction potentials of azurin mutants is shown, based on a combination of continuum electrostatics, density functional theory and empirical hydrophobicity factors. Our method accurately reproduces experimental reduction potential changes of 30 mutants with respect to wildtype within experimental error and highlights the factors contributing to the reduction potential change. Finally, reduction potentials are predicted for a series of 124 new mutants that have not yet been investigated experimentally. Several mutants are identified that are located well over 10 Å from the copper center that change the reduction potential by more than 85 mV. The work shows that secondary coordination sphere mutations mostly lead to long‐range electrostatic changes and hence can be modeled accurately with continuum electrostatics.
Viologens and Their Application as Functional Materials
Authors: Striepe Laura , Baumgartner Thomas
Published: August 2017

Organic materials have recently gained considerable attention for electronic applications, improving performance and sustainability to current technologies. Commercialized metal‐based systems are generally expensive, toxic and difficult to recycle, however organic materials offer promising solutions. Viologens,N,N′ di‐quaternized bipyridyl salts, are a well‐studied species exhibiting three reversible redox states, possessing valuable electrochromic and electron‐accepting properties. These properties can be fine‐tuned through synthesis by altering the nitrogen substituents and various counteranions. Currently, viologens have become of great interest as functional materials in a wide array of applications; a few to name include electrochromic devices, molecular machines, and organic batteries. This review highlights representative recent work and advances towards utilizing viologens in practical applications that currently compete with metal‐based technologies. Additionally, modified viologens that can be further fine‐tuned will be discussed.
Drug development for breast, colorectal, and non–small cell lung cancers from 1979 to 2014
Authors: Nixon Nancy A. , Khan Omar F. , Imam Hasiba , Tang Patricia A. , Monzon Jose , Li Haocheng , Sun Gavin , Ezeife Doreen , Parimi Sunil , Dowden Scot , Tam Vincent C.
Published: August 2017

BACKGROUND

Understanding the drug development pathway is critical for streamlining the development of effective cancer treatments. The objective of the current study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites.

METHODS

Drugs entering clinical trials for breast, colorectal, and non–small cell lung cancer were identified using a pharmaceutical business intelligence database. Data regarding drug characteristics, clinical trials, and approval dates were obtained from the database, clinical trial registries, PubMed, and regulatory Web sites.

RESULTS

A total of 411 drugs met the inclusion criteria for breast cancer, 246 drugs met the inclusion criteria for colorectal cancer, and 315 drugs met the inclusion criteria for non–small cell lung cancer. Attrition rates were 83.9% for breast cancer, 87.0% for colorectal cancer, and 92.0% for non–small cell lung cancer drugs. In the case of non–small cell lung cancer, there was a trend toward higher attrition rates for targeted monoclonal antibodies compared with other agents. No tumor site‐specific differences were noted with regard to cytotoxic chemotherapy, immunomodulatory, or small molecule kinase inhibitor drugs. Drugs classified as “others” in breast cancer had lower attrition rates, primarily due to the higher success of hormonal medications. Mean drug development times were 8.9 years for breast cancer, 6.7 years for colorectal cancer, and 6.6 years for non–small cell lung cancer.

CONCLUSIONS

Overall oncologic drug attrition rates remain high, and drugs are more likely to fail in later‐stage clinical trials. The refinement of early‐phase trial design may permit the selection of drugs that are more likely to succeed in the phase 3 setting. Cancer 2017;123:4672‐4679. © 2017 American Cancer Society.
Second‐line treatment in patients with pancreatic ductal adenocarcinoma: A meta‐analysis
Authors: Sonbol Mohamad Bassam , Firwana Belal , Wang Zhen , Almader‐Douglas Diana , Borad Mitesh J. , Makhoul Issam , Ramanathan Ramesh K. , Ahn Daniel H. , Bekaii‐Saab Tanios
Published: August 2017

BACKGROUND

There are limited therapeutic options for treatment‐refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine‐based regimens. The authors performed a meta‐analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first‐line treatment progression in patients with PDAC.

METHODS

Different databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first‐line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared with FP. Outcomes of interest included overall survival (OS) and progression‐free survival (PFS).

RESULTS

Five studies with 895 patients were identified. Patients randomized to receive FPIRI/FPOX had a significantly improved PFS and a trend toward improved OS compared with those who received FP monotherapy. When comparing FPIRI with FP, there was an improvement in both PFS (hazard ratio, 0.64; 95% confidence interval, 0.47‐0.87; P = .005) and OS (hazard ratio, 0.70; 95% confidence interval, 0.55‐0.89; P = .004) in patients who received the combination. Conversely, FPOX produced only a modest improvement in PFS with no improvement in OS.

CONCLUSIONS

Combination chemotherapy with OX or various IRI formulations appears to improve PFS compared with single‐agent FP. FPIRI, but not FPOX, appears to confer an OS advantage. The combination of FP with irinotecan formulations appears to be the appropriate next line of treatment upon progression after gemcitabine‐based chemotherapy regimens. Cancer 2017;123:4680‐4686. © 2017 American Cancer Society.
Design and optimization of hybrid resonant loops for efficient wireless power transfer
Authors: Wang Meng , Shi Yanyan , Gao Weikang , Shen Minghui , Shen Mingsheng
Published: August 2017

Frequency splitting, caused by magnetic overcoupling, is a great challenge in resonant wireless power transfer, which leads to decrease of transfer efficiency. In this paper, to avoid the frequency splitting, a new design of hybrid resonant loops with an inner coil positioned in the transmitter is proposed for efficient power transfer. It is shown to suppress dramatic variation of mutual inductance when the distance between transmitter and receiver decreases. Analytical expressions of the mutual inductance and the transfer efficiency for the proposed resonant wireless power transfer system are calculated. To obtain a relatively uniform mutual inductance with respect to the distance, the proposed resonant loops are optimized. Simulation and experiments are also performed to validate the effectiveness of the proposed resonant loops in eliminating the frequency splitting. The transfer efficiency remains higher than 80% when the transfer distance decreases below a critical value where frequency splitting occurs for conventional resonant loops. Furthermore, lateral and angular misalignments between the resonant loops are also considered and investigated. The results indicate that the proposed resonant loops are also applicable in suppressing the frequency splitting even in case of misalignments.
Expanding exposure‐based interventions for eating disorders
Authors: Reilly Erin E. , Anderson Lisa M. , Gorrell Sasha , Schaumberg Katherine , Anderson Drew A.
Published: August 2017

Initial trials evaluating exposure‐based interventions for eating disorders (EDs) in the 1980s demonstrated mixed results. Since that time, innovations in exposure therapy for anxiety disorders have yielded insights that can be used to refine and expand the approach to effectively target ED behaviors. This article provides a brief summary of relevant advances in exposure therapy for anxiety and outlines how these advances may be adapted and evaluated for use with ED samples. More specifically, we propose shifting to an inhibitory learning framework, considering treatment targets other than fear, and increasing variability in exposure techniques represent three important areas for future study. Overall, this article aims to provide professionals in the field with a framework for how to incorporate cutting‐edge advances in exposure therapy into rigorous intervention research for EDs.
Protonation of Coordinated Dinitrogen Using Protons Generated from Molecular Hydrogen
Authors: Tamizmani Masilamani , Sivasankar Chinnappan
Published: August 2017

A new strategy has been developed to synthesize N–H bonds from coordinated N2 in trans‐[W(dppe)2(N2)2] (1) using protons generated from H2 in the presence of (C6F5)3B and 2,2,6,6‐tetramethylpiperidine, under normal experimental conditions or upon sonication. The complexes [(dppe)2WH(NNH2)][HB(C6F5)3] (2) and [FW(dppe)2(NNH2)][HB(C6F5)3] (3) have been successfully isolated and characterized using standard analytical and spectroscopic methods. We have also monitored the progress of the reaction of complex 1 with a frustrated Lewis pair dihydrogen adduct (FLP‐H2) using standard spectroscopic techniques by following the signatures of the reactants and the products. The results of the current studies are promising for fixing N2 into ammonia by using H2, under normal experimental conditions, in the near future.
Stereocontrolled Access to Benzo‐Annelated all‐cis‐ and cis,cis,cis,trans‐[5.5.5.6]Fenestranones and all‐cis‐[5.5.5.5]Fenestranes
Authors: Bredenkötter Björn , Linke Jens , Kuck Dietmar
Published: August 2017

The synthesis of three multiply substituted fenestrindanes (all‐cis‐tetrabenzo[5.5.5.5]fenestranes) is described in detail. Depending on the stereochemical course of the twofold Michael addition of a 1,3‐indanedione to a dibenzylideneacetone in the very first step, the corresponding all‐cis‐tribenzo[5.5.5.6]fenestranones or the strained cis,cis,cis,trans isomers are obtained. In the latter case, stereochemical adjustment to the all‐cis configuration can be achieved by base‐induced epimerization. Conversion of the all‐cis‐[5.5.5.6]fenestranones in five subsequent steps affords the target fenestrindanes bearing either methyl groups at four of the inner (bay) positions or methoxy groups at four or six of the outer (peripheral) positions of the molecular framework.
Map the gap: alternative visualisations of geographic knowledge production
Authors: Walker Margath , Frimpong Boamah Emmanuel
Published: August 2017

The main purpose of this paper is to develop a new method for visualizing knowledge production which is attentive to the multiple elements embedded in research processes. In particular, we seek to problematise the representation of scholarship indicators by depicting theoretical contributions and field sites along a spectrum, rather than as discrete points, recursively and relationally constituted. The primary aim of our visualisations is to capture text and context, and codified and tacit knowledge. First, we offer a conventional representation of the location of selected dominant critical theories in Geography, arguing that current methods reinforce ‘lopsided’ geographies of knowledge production. Normative practices of data visualisation and representation captured in our two examples privilege certain elements centred on authorship and tend to silence the contexts informing research. Second, we borrow the term and method of chromatography, a tool used in the natural sciences but here conceived in its more literal sense of ‘writing the separations’. Our ‘chromatographical’ representations attempt to unbundle components currently absorbed by formal indicators of knowledge production. Such counter mappings attempt to convey the relational aspect of research between countries imbricated in the propagation of exemplary critical geographic theories. We conclude with a discussion of the implications that the disaggregation of value has for scholars and their research.
Changes to white matter microstructure in transient ischemic attack: A longitudinal diffusion tensor imaging study
Authors: Ferris Jennifer K. , Edwards Jodi D. , Ma Jennifer A. , Boyd Lara A.
Published: August 2017

Transient ischemic attack (TIA) is associated with localized ischemic changes, identifiable by diffusion‐weighted imaging. Past research has not considered whether TIA is also associated with diffuse changes to white matter microstructure; further past work has not tracked changes longitudinally. Here we examine whole‐brain changes in fractional anisotropy (FA) in individuals with TIA presenting with sensorimotor symptoms. Twenty individuals with a recent (within 30 days) TIA and 12 healthy older adults were recruited. Participants underwent 3.0 T diffusion MRI at baseline; scans were repeated for the TIA group 90 days post‐TIA. Track‐based spatial statistics (TBSS) was used to conduct a voxel‐wise analysis of FA between groups. FA was significantly lower in the TIA group relative to healthy controls, primarily in anterior white matter tracts including: forceps minor, anterior thalamic radiations, cingulum, inferior fronto‐occipital fasciculus, and corticospinal tract. TBSS results informed an ROI‐based longitudinal examination of FA in the TIA group. There were no changes to TBSS‐identified clusters, forceps minor, or the corticospinal tract over time. There was lower FA in the anterior thalamic radiations in the TIA‐affected hemisphere at baseline, but no difference between hemispheres at 90 days. In summary, individuals with TIA presenting with sensorimotor symptoms have decreased FA in tracts that are also implicated in sensorimotor function, which outlast the clinical symptoms associated with TIA. This suggests a more profound type of brain damage associated with TIA than has been typically described in past work. Diffusion tensor imaging may have utility as a marker of TIA‐associated changes to white matter pathways. Hum Brain Mapp 38:5795–5803, 2017. © 2017 Wiley Periodicals, Inc.
External jugular veno‐accompanying artery adipofascial flap: A novel and convenient flap for head and neck reconstruction
Authors: Park Seong Oh , Ahn Kyung Chan , Hong Ki Yong , Chang Hak , Imanishi Nobuaki
Published: August 2017

Background

The veno‐accompanying artery adipofascial (VAF) flap is nourished by accompanying vessels near large superficial veins. We examined whether the VAF flap can be applied to the external jugular vein.

Methods

Based on anatomic and angiographic studies, we performed reconstructive surgeries using external jugular veno‐accompanying artery adipofascial (EJ‐VAF) flaps. A retrospective chart review was performed for all patients who underwent this surgery.

Results

The presence of arteries accompanying the external jugular vein was confirmed. The presence of source arteries was also confirmed. These included the occipital, facial, and superior thyroid arteries. All patients had satisfactory outcomes, except for 1 patient who had partial necrosis, which was managed using conservative treatment.

Conclusion

Our anatomic and angiographic studies in this clinical series indicate that the EJ‐VAF flap is a reliable and convenient flap. Thus, it is useful in reconstruction of small to medium head and neck defects.
Evaluation of incidence, significance, and prognostic role of circulating tumor microemboli and transforming growth factor‐β receptor I in head and neck cancer
Authors: Fanelli Marcello Ferretti , Oliveira Thiago Bueno , Braun Alexcia Camila , Corassa Marcelo , Abdallah Emne Ali , Nicolau Ulisses Ribaldo , da Silva Alves Vanessa , Garcia Daniel , Calsavara Vinicius F. , Kowalski Luiz Paulo , Chinen Ludmilla Thomé Domingos
Published: August 2017

Background

Circulating tumor microemboli (CTM) are clusters of circulating tumor cells (CTCs), involved in metastasis, as also transforming growth factor‐β (TGF‐β). The purpose of this study was to verify their role in progression‐free survival (PFS).

Methods

Blood from patients with locally advanced head and neck squamous cell carcinoma (HNSCC; n = 53) was analyzed in 2 moments. TGF‐β receptor I (TGF‐βRI) expression was evaluated by immunocytochemistry.

Results

Comparing CTM1 (baseline) with CTM2 (first follow‐up), patients with CTM1‐positive disease who became CTM2‐negative were classified as favorable (PFS 20 months). Patients with unfavorable evolution (CTM1‐negative/CTM2‐positive), had PFS of 17.5 months. Patients always CTM‐negative showed PFS of 22.4 months, those always positive, 4.7 months (P < .001). The TGF‐βRI expression in the first follow‐up correlated with poor PFS (12 × 26 months; P = .007), being an independent prognostic factor (hazard ratio [HR] = 6.088; P =  .033).

Conclusion

CTM1/2, TGF‐βRI expression, and unfavorable CTM kinetics may represent poor prognosis in locally advanced HNSCC.
pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI
Authors: Pavuluri KowsalyaDevi , McMahon Michael T.
Published: August 2017

Acid‐base homeostasis is an essential process for maintaining proper pH levels in the body, with alterations in this process potentially signaling pathology. While monitoring urine pH, blood gases and other assays can provide information on the overall systemic pH, it is desirable to get more localized knowledge to assist diagnosis. Various non‐invasive methods have been developed with Chemical Exchange Saturation Transfer (CEST) MRI now emerging as a particularly intriguing technology for detecting pH. In this review, we provide an overview of the paramagnetic and diamagnetic CEST probes available for producing pH maps, describe in depth the various methods to collect CEST MRI data and post‐process the resulting images to create pH maps and describe how this has been applied for detecting renal injury, mapping the pH of tumors and monitoring the health of transplanted therapeutic cells. Finally, we will provide an outlook of the possibilities to translate this technology into patients.
Detection and diagnosis of meningioma brain tumor using ANFIS classifier
Authors: Kathirvel R. , Batri K.
Published: August 2017

Tumors are formed in brain due to the uncontrolled development of cells. These tumors can be cured if it is timely detected and by proper medication. This article proposes a computer‐aided automatic detection and diagnosis of meningioma brain tumors in brain images using Adaptive Neuro Fuzzy Inference System (ANFIS) classifier. The proposed system consists of feature extraction, classification, and segmentation and diagnosis sections. In this article, Grey level Co‐occurrence Matric (GLCM) and Grid features are extracted from the brain image and these features are classified using ANFIS classifier into normal or abnormal. Then, morphological operations are used to segment the abnormal regions in brain image. Based on the location of these abnormal regions in brain tissues, the segmented tumor regions are diagnosed.
Analysis of denoising filters on MRI brain images
Authors: Saladi Saritha , Amutha Prabha N.
Published: August 2017

The magnetic resonance imaging (MRI) modality is an effective tool in the diagnosis of the brain. These MR images are introduced with noise during acquisition which reduces the image quality and limits the accuracy in diagnosis. Elimination of noise in medical images is an important task in preprocessing and there exist different methods to eliminate noise in medical images. In this article, different denoising algorithms such as nonlocal means, principal component analysis, bilateral, and spatially adaptive nonlocal means (SANLM) filters are studied to eliminate noise in MR. Comparative analysis of these techniques have been with help of various metrics such as signal‐to‐noise ratio, peak signal‐to‐noise ratio (PSNR), mean squared error, root mean squared error, and structure similarity (SSIM). This comparative study shows that the SANLM denoising filter gives the best performance in terms of better PSNR and SSIM in visual interpretation. It also helps in clinical diagnosis of the brain.
An efficient and automatic glioblastoma brain tumor detection using shift‐invariant shearlet transform and neural networks
Authors: Arunachalam Murugan , Royappan Savarimuthu Sabeenian
Published: August 2017

The detection and segmentation of tumor region in brain image is a critical task due to the similarity between abnormal and normal region. In this article, a computer‐aided automatic detection and segmentation of brain tumor is proposed. The proposed system consists of enhancement, transformation, feature extraction, and classification. The shift‐invariant shearlet transform (SIST) is used to enhance the brain image. Further, nonsubsampled contourlet transform (NSCT) is used as multiresolution transform which transforms the spatial domain enhanced image into multiresolution image. The texture features from grey level co‐occurrence matrix (GLCM), Gabor, and discrete wavelet transform (DWT) are extracted with the approximate subband of the NSCT transformed image. These extracted features are trained and classified into either normal or glioblastoma brain image using feed forward back propagation neural networks. Further, K‐means clustering algorithm is used to segment the tumor region in classified glioblastoma brain image. The proposed method achieves 89.7% of sensitivity, 99.9% of specificity, and 99.8% of accuracy.
Fusion of MRI and CT images using guided image filter and image statistics
Authors: Bavirisetti Durga Prasad , Kollu Vijayakumar , Gang Xiao , Dhuli Ravindra
Published: August 2017

In medical imaging using different modalities such as MRI and CT, complementary information of a targeted organ will be captured. All the necessary information from these two modalities has to be integrated into a single image for better diagnosis and treatment of a patient. Image fusion is a process of combining useful or complementary information from multiple images into a single image. In this article, we present a new weighted average fusion algorithm to fuse MRI and CT images of a brain based on guided image filter and the image statistics. The proposed algorithm is as follows: detail layers are extracted from each source image by using guided image filter. Weights corresponding to each source image are calculated from the detail layers with help of image statistics. Then a weighted average fusion strategy is implemented to integrate source image information into a single image. Fusion performance is assessed both qualitatively and quantitatively. Proposed method is compared with the traditional and recent image fusion methods. Results showed that our algorithm yields superior performance.
Quantitative susceptibility mapping in a diabetes mellitus rat model: Iron accumulation in the brain
Authors: Yoon Soo‐Young , Park Soonchan , Kim Hyug‐Gi , Park Tae‐Hee , Kim Sun Mi , Hwang You‐Cheol , Kim Gou Young , Ryu Chang‐Woo , Yoon Tai‐Young , Jahng Geon‐Ho
Published: August 2017

This study evaluated the susceptibility effects using quantitative susceptibility mapping (QSM) as a marker for regional brain iron alternations in diabetic rat brains. Otsuka Long‐Evans Tokushima Fatty (OLETF) rats (n = 7) and age‐matched lean Long‐Evans Tokushima Otsuka (LETO) control rats (n = 8) were scanned using a three‐dimensional gradient‐echo sequence in a 3 Tesla MRI to map QSM. The correlation analysis was performed to evaluate the relationship between the QSM value and the body weight and the fasting blood glucose value of the rats. QSM values in the OLETF group were significantly increased in hippocampi and thalami, as compared with those of the LETO group. The QSM values of the OLETF rats were negatively correlated with the body weight in putamen and were significantly correlated with the fasting blood glucose level in the left amygdala and right thalamus. With higher QSM values in diabetic rats than in control rats, QSM values in the diabetic group were significantly correlated with the body weight and the fasting blood glucose level, indicating that the QSM technique should be helpful to noninvasively investigate iron overload in the diabetic brain.
NOX4‐ and Nrf2‐mediated oxidative stress induced by silver nanoparticles in vascular endothelial cells
Authors: Sun Xia , Yang Yi , Shi Junpeng , Wang Chengcheng , Yu Zhenfeng , Zhang Hongwu
Published: August 2017

It has been widely reported that silver nanoparticles (AgNPs) induce oxidative stress in various cell lines. However, the mechanism for this effect and its consequences for cellular signaling are poorly understood. In this study, human umbilical vein endothelial cells (HUVECs) were used to assess the toxicity and investigate the associated molecular mechanisms caused by exposure to AgNPs. We demonstrated that AgNP exposure significantly and dose‐dependently decreased the cell viability, induced reactive oxygen species (ROS) generation and led to early apoptosis in HUVECs. Our findings showed that AgNPs induced excess ROS production that affected the signaling pathways by a mechanism that depended on activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity through upregulation of NADPH oxidase 4 (NOX4) protein expressions. Moreover, AgNPs could disrupt the inactivation of the nuclear factor erythroid 2‐related factor 2 (Nrf2)‐mediated antioxidant response, which is considered another important element for oxidative stress caused by AgNPs in HUVECs. The redox imbalance between NOX4 and Nrf2 was an important cause for the ROS overproduction that led to cell injury in HUVECs. The results provided insight into the mechanisms of oxidative stress induced by AgNPs in vascular endothelial cells.
Inhibitory effects of oxytocin and oxytocin receptor antagonist atosiban on the activities of carbonic anhydrase and acetylcholinesterase enzymes in the liver and kidney tissues of rats
Authors: Kocyigit Umit M. , Taşkıran Ahmet Şevki , Taslimi Parham , Yokuş Ahmet , Temel Yusuf , Gulçin İlhami
Published: August 2017

The aim of this study was to investigate the effects of oxytocin (OT), atosiban, which is an OT receptor antagonist, and OT‐atosiban chemicals injected to rats on the activities of carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes in liver and kidney tissues of rats. For this purpose, four different groups, each consisting of six rats (n = 6), were formed (control group, OT administered group, atosiban administered group, and both OT and atosiban administered group). The rats were necropsied 60 min after intraperitoneal injection of chemicals into the rats. Liver tissues of rats were extracted. CA and AChE enzyme activities were measured for each tissue by using hydratase, esterase, and acetylcholiniodide methods. Activity values for each enzyme obtained were statistically calculated.
A prognostic 11 genes expression model for ovarian cancer
Authors: Men Chuan‐Di , Liu Qiong‐Na , Ren Qing
Published: August 2017

The symptoms of ovarian cancer at early stages are usually absent which makes the diagnosis in its early stages exceedingly difficult. Previous research has proven that ovarian cancer is a genetic disease, which depends on the alteration of multi‐cancer related genes and anti‐cancer genes, multi‐stages and multi‐pathways, involving a variety of oncogene activation and anti‐oncogene inactivation. For a better understanding of the prognostic classification of ovarian cancer, gene expression profiles were used to analyze the prognostic factors of ovarian cancer, and the prognostic model was used to classify the ovarian cancer samples. The ovarian cancer samples data were downloaded from TCGA dataset. Rebust likelihood‐based survival model was built to find the key genes that could function as prognostic markers. The samples were classified by unsupervised hierarchical clustering. Furthermore, Kaplan‐Meier survival analysis was used to analyze the differences in the prognosis of the samples. The prognostic model was used to classify the samples, and then the best classification model was selected as the prognostic model of ovarian cancer. Finally, GEO datasets were used for external data validation. A total of 886 genes with influence on prognosis was obtained. Then genomic combinations of 11 genes were screened out by random sampling. Then the active number of influential factors was counted based on the expression level of featured genes. When the number of influencing factors is ≥7, the prognosis difference among these genes is the largest (P‐value = 0.000775); and this was chosen as the final Classification model. To summary, a prognostic 11genes expression model was preliminarily built to classify the ovarian cancer samples.
Key developments that impacted the field of mechanobiology and mechanotransduction
Authors: Wall Michelle , Butler David , El Haj Alicia , Bodle Josephine C. , Loboa Elizabeth G. , Banes Albert J.
Published: August 2017

Advances in mechanobiology have evolved through insights from multiple disciplines including structural engineering, biomechanics, vascular biology, and orthopaedics. In this paper, we reviewed the impact of key reports related to the study of applied loads on tissues and cells and the resulting signal transduction pathways. We addressed how technology has helped advance the burgeoning field of mechanobiology (over 33,600 publications from 1970 to 2016). We analyzed the impact of critical ideas and then determined how these concepts influenced the mechanobiology field by looking at the citation frequency of these reports as well as tracking how the overall number of citations within the field changed over time. These data allowed us to understand how a key publication, idea, or technology guided or enabled the field. Initial observations of how forces acted on bone and soft tissues stimulated the development of computational solutions defining how forces affect tissue modeling and remodeling. Enabling technologies, such as cell and tissue stretching, compression, and shear stress devices, allowed more researchers to explore how deformation and fluid flow affect cells. Observation of the cell as a tensegrity structure and advanced methods to study genetic regulation in cells further advanced knowledge of specific mechanisms of mechanotransduction. The future of the field will involve developing gene and drug therapies to simulate or augment beneficial load regimens in patients and in mechanically conditioning organs for implantation. Here, we addressed a history of the field, but we limited our discussions to advances in musculoskeletal mechanobiology, primarily in bone, tendon, and ligament tissues. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:605–619, 2018.
Simple and sensitive determination of malondialdehyde in human urine and saliva using UHPLC–MS/MS after derivatization with 3,4‐diaminobenzophenone
Authors: Oh Jin‐Aa , Shin Ho‐Sang
Published: August 2017

Malondialdehyde has been used as a biomarker for lipid peroxidation in biological samples. An ultra‐high performance liquid chromatography with tandem mass spectrometry method was developed to determine the levels of malondialdehyde in human urine and saliva samples. To select the optimum derivatization reagent from four diamino compounds, the reactivity and sensitivity of their derivatives were compared, and 3,4‐diaminobenzophenone was selected. The optimum reaction conditions for malondialdehyde with 3,4‐diaminobenzophenone were as follows: a reagent dosage of 50 mg/L, pH of 4, and reaction for 30 min at 50°C. The formed derivative product was analyzed using ultra‐high performance liquid chromatography with tandem mass spectrometry without additional extraction or concentration steps. In the optimal conditions, the method was used to determine malondialdehyde concentration in human urine and saliva samples. The limits of quantification for malondialdehyde in biological samples were over a concentration range of 0.1–0.3 μg/L. Additionally, the calibration curve showed a linearity greater than r2 = 0.997. The method was used to analyze 14 human urine and saliva samples from healthy volunteers. Malondialdehyde was detected in the concentration range of 1.7–33.6 μg/g creatinine in all human urine samples and 0.1–1.3 μg/L in all human saliva samples.
The hidden costs of control revisited: Should a sanctioning policy be announced in advance?
Authors: Klempt Charlotte , Pull Kerstin
Published: August 2017

Sanctions are widely used to enhance compliance in principal agent relationships. Although there is ample evidence confirming the predicted positive incentive effect of sanctions, it has also been shown that imposing sanctions may reduce compliance by crowding out intrinsic motivation. We add to the literature on the hidden costs of control by showing that these costs are restricted to situations where the principal actively chooses to sanction low performance and where this choice is known to the agent. In such a situation, the principal's commitment to sanction low performance might indicate that she or he is a distrustful “type” and hence conveys a negative signal. To the contrary, if (a) an agent is not informed about whether low performance will be sanctioned or if (b) the computer determines whether low performance will be sanctioned, the principal's “type” is not revealed, and we find no evidence of crowding out.
On the chemical meaning of some growth models possessing Gompertzian‐type property
Authors: Anguelov Roumen , Borisov Milen , Iliev Anton , Kyurkchiev Nikolay , Markov Svetoslav
Published: August 2017

Growth models are often used when modelling various processes in life sciences, ecology, demography, social sciences, etc. Dynamical growth models are usually formulated in terms of an ODE (system of ODS's) or by an explicit solution to an ODE, such as the logistic, Gompertz, and Richardson growth models. To choose a suitable growth model it is useful to know the physics‐chemical meaning of the model. In many situations this meaning is best expressed by means of a reaction network that possibly induces the dynamical growth model via mass action kinetics. Such reaction networks are well known for a number of growth models, such as the saturation‐decay and the logistic Verhulst models. However, no such reaction networks exist for the Gompertz growth model. In this work we propose some reaction networks using mass action kinetics that induce growth models that are (in certain sense) close to the Gompertz model. The discussion of these reaction networks aims to a better understanding of the chemical properties of the Gompertz model and “Gompertzian‐type” growth models. Our method can be considered as an extension of the work of previous authors who “recasted” the Gompertz differential equation into a dynamical system of two differential equations that, apart of the basic species variable, involve an additional variable that can be interpreted as a “resource.” Two new growth models based on mass action kinetics are introduced and studied in comparison with the Gompertz model. Numerical computations are presented using some specialized software tools.
Uniform regularity and vanishing viscosity limit for the chemotaxis‐Navier‐Stokes system in a 3D bounded domain
Authors: Zhang Zhipeng
Published: August 2017

We investigate the uniform regularity and vanishing viscosity limit for the incompressible chemotaxis‐Navier‐Stokes system with Navier boundary condition for velocity field and Neumann boundary condition for cell density and chemical concentration in a 3D bounded domain. It is shown that there exists a unique strong solution of the incompressible chemotaxis‐Navier‐Stokes system in a finite time interval, which is independent of the viscosity coefficient. Moreover, this solution is uniformly bounded in a conormal Sobolev space, which allows us to take the vanishing viscosity limit to obtain the incompressible chemotaxis‐Euler system.
An inverse problem for a family of two parameters time fractional diffusion equations with nonlocal boundary conditions
Authors: Ali Muhammad , Malik Salman A.
Published: August 2017

The determination of a space‐dependent source term along with the solution for a 1‐dimensional time fractional diffusion equation with nonlocal boundary conditions involving a parameter β>0 is considered. The fractional derivative is generalization of the Riemann‐Liouville and Caputo fractional derivatives usually known as Hilfer fractional derivative. We proved existence and uniqueness results for the solution of the inverse problem while over‐specified datum at 2 different time is given. The over‐specified datum at 2 time allows us to avoid initial condition in terms of fractional integral associated with Hilfer fractional derivative.
Effect of Dietary Components from Antarctic Krill on Atherosclerosis in apoE‐Deficient Mice
Authors: Parolini Cinzia , Bjorndal Bodil , Busnelli Marco , Manzini Stefano , Ganzetti Giulia S. , Dellera Federica , Ramsvik Marie , Bruheim Inge , Berge Rolf Kristian , Chiesa Giulia
Published: August 2017

Scope

Antarctic krill is a great source of n‐3 fatty acids and high‐quality proteins. Aim of the study was to evaluate the effect of Antarctic krill components on plasma lipids and atherosclerosis development.

Methods and results

Sixty apoEKO mice were divided into four groups and fed Western diet (CONTROL) or Western‐like diets, differing for protein or fat content. Specifically, casein or fat in CONTROL was partially replaced by krill proteins (PRO), krill oil (KRILL OIL), or both (KRILL OIL+PRO). In KRILL OIL+PRO and KRILL OIL, cholesterol levels were significantly lower than in CONTROL group. Atherosclerosis in aorta of PRO, KRILL OIL and KRILL OIL+PRO was lower than in CONTROL, whereas, at the aortic sinus, atherosclerosis reduction was only observed in KRILL OIL. Liver steatosis, commonly present in CONTROL and PRO animals, was sporadic in KRILL OIL+PRO and KRILL OIL mice. Krill oil containing diets affected the expression of genes involved in cholesterol metabolism, mainly HMG‐CoA reductase. No reduced systemic inflammation was found in all groups.

Conclusion

Krill oil containing diets were able to reduce cholesterol levels, inhibit plaque development and prevent liver damage. Krill proteins also reduced atherosclerosis development through mechanisms not involving lipid metabolism.
Metabolite‐cycled STEAM and semi‐LASER localization for MR spectroscopy of the human brain at 9.4T
Authors: Giapitzakis Ioannis‐Angelos , Shao Tingting , Avdievich Nikolai , Mekle Ralf , Kreis Roland , Henning Anke
Published: August 2017

Purpose

Metabolite cycling (MC) is an MRS technique for the simultaneous acquisition of water and metabolite spectra that avoids chemical exchange saturation transfer effects and for which water may serve as a reference signal or contain additional information in functional or diffusion studies. Here, MC was developed for human investigations at ultrahigh field.

Methods

MC‐STEAM and MC‐semi‐LASER are introduced at 9.4T with an optimized inversion pulse and elaborate coil setup. Experimental and simulation results are given for the implementation of adiabatic inversion pulses for MC. The two techniques are compared, and the effect of frequency and phase correction based on the MC water spectra is evaluated. Finally, absolute quantification of metabolites is performed.

Results

The proposed coil configuration results in a maximum
of 48 μΤ in a voxel within the occipital lobe. Frequency and phase correction of single acquisitions improve signal‐to‐noise ratio (SNR) and linewidth, leading to high‐resolution spectra. The improvement of SNR of N‐acetylaspartate (SNRNAA) for frequency aligned data, acquired with MC‐STEAM and MC‐semi‐LASER, are 37% and 30%, respectively (P < 0.05). Moreover, a doubling of the SNRNAA for MC‐semi‐LASER in comparison with MC‐STEAM is observed (P < 0.05). Concentration levels for 18 metabolites from the human occipital lobe are reported, as acquired with both MC‐STEAM and MC‐semi‐LASER.

Conclusion

This work introduces a novel methodology for single‐voxel MRS on a 9.4T whole‐body scanner and highlights the advantages of semi‐LASER compared to STEAM in terms of excitation profile. In comparison with MC‐STEAM, MC‐semi‐LASER yields spectra with higher SNR. Magn Reson Med 79:1841–1850, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Thermal response of carbon fiber epoxy laminates with metallic and nonmetallic protection layers to simulated lightning currents
Authors: Lee Juhyeong , Lacy Thomas E. , Pittman Charles U. , Mazzola Michael S.
Published: August 2017

Nonlinear finite element (FE) simulations to characterize lightning‐induced thermal damage in AS4/3506 carbon/epoxy composites with metallic and nonmetallic protection layers were performed and then compared with those for unprotected composites. In this study, FE estimates of matrix thermal decomposition in composites subjected to 40 kA peak currents were performed. Two protection layers were considered: (1) a traditional copper mesh (CM) commonly used for aircraft lightning strike protection and (2) a single layer of highly conductive pitch carbon fiber paper (PCFP). Temperature‐dependent material properties of each constituent were used to predict the matrix thermal decomposition induced by simulated lightning current waveforms. The lightning strike FE models suggest that both the CM and the PCFP lightning protection layers successfully mitigated thermal damage development in the underlying composites as a consequence of reduced through‐thickness electrical current flow/heat conduction. The CM provided excellent protection from thermal damage; the predicted matrix decomposition only penetrated the first AS4/3506 ply. Similarly, the PCFP outer layer limited thermal damage to the top three composite plies, while the predicted matrix decomposition of the unprotected composite penetrated the sixth ply. Improved PCFP protection layers appear possible to design by varying the in‐plane and through‐thickness electrical conductivities, as well as the PCFP‐to‐first ply gap conductance. This suggests that PCFP outer layers or similar lightweight carbon‐based layers may serve as efficient lightning protection layers. POLYM. COMPOS., 39:E2149–E2166, 2018. © 2017 Society of Plastics Engineers