bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitric Oxide Reverses the Position of the Heart during Embryonic Development
Authors: Siamwala Jamila , Kumar Pavitra , Veeriah Vimal , Muley Ajit , Rajendran Saranya , Konikkat Salini , Majumder Syamantak , Mani Krishna , Chatterjee Suvro
Published: March 2019

Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) plays crucial roles in cardiac homeostasis. Adult cardiomyocyte specific overexpression of eNOS confers protection against myocardial-reperfusion injury. However, the global effects of NO overexpression in developing cardiovascular system is still unclear. We hypothesized that nitric oxide overexpression affects the early migration of cardiac progenitor cells, vasculogenesis and function in a chick embryo. Vehicle or nitric oxide donor DEAN (500 µM) were loaded exogenously through a small window on the broad side of freshly laid egg and embryonic development tracked by live video-microscopy. At Hamburg Hamilton (HH) stage 8, the cardiac progenitor cells (CPC) were isolated and cell migration analysed by Boyden Chamber. The vascular bed structure and heart beats were compared between vehicle and DEAN treated embryos. Finally, expression of developmental markers such as BMP4, Shh, Pitx2, Noggin were measured using reverse transcriptase PCR and in-situ hybridization. The results unexpectedly showed that exogenous addition of pharmacological NO between HH stage 7–8 resulted in embryos with situs inversus in 28 out of 100 embryos tested. Embryos treated with NO inhibitor cPTIO did not have situs inversus, however 10 embryos treated with L-arginine showed a situs inversus phenotype. N-acetyl cysteine addition in the presence of NO failed to rescue situs inversus phenotype. The heart beat is normal (120 beats/min) although the vascular bed pattern is altered. Migration of CPCs in DEAN treated embryos is reduced by 60% compared to vehicle. BMP4 protein expression increases on the left side of the embryo compared to vehicle control. The data suggests that the NO levels in the yolk are important in turning of the heart during embryonic development. High levels of NO may lead to situs inversus condition in avian embryo by impairing cardiac progenitor cell migration through the NO-BMP4-cGMP axis.
Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells
Authors: Soltan Marwa Y. , Sumarni Uly , Assaf Chalid , Langer Peter , Reidel Ulrich , Eberle Jürgen
Published: March 2019

Cutaneous T-cell lymphoma (CTCL) may develop a highly malignant phenotype in its late phase, and patients may profit from innovative therapies. The plant extract indirubin and its chemical derivatives represent new and promising antitumor strategies. This first report on the effects of an indirubin derivative in CTCL cells shows a strong decrease of cell proliferation and cell viability as well as an induction of apoptosis, suggesting indirubin derivatives for therapy of CTCL. As concerning the mode of activity, the indirubin derivative DKP-071 activated the extrinsic apoptosis cascade via caspase-8 and caspase-3 through downregulation of the caspase antagonistic proteins c-FLIP and XIAP. Importantly, a strong increase of reactive oxygen species (ROS) was observed as an immediate early effect in response to DKP-071 treatment. The use of antioxidative pre-treatment proved the decisive role of ROS, which turned out upstream of all other proapoptotic effects monitored. Thus, reactive oxygen species appear as a highly active proapoptotic pathway in CTCL, which may be promising for therapeutic intervention. This pathway can be efficiently activated by an indirubin derivative.
VKORC1 and CYP2C9 Polymorphisms: A Case Report in a Dutch Family with Pulmonary Fibrosis
Authors: Wijnen Petal , Drent Marjolein , Bekers Otto , Verschakelen Johny , Bast Aalt
Published: March 2019

Here, we describe a Dutch family with idiopathic pulmonary fibrosis (IPF). We hypothesized that there might be an association between the presence of Vitamin K epoxide reductase complex 1 (VKORC1) and/or cytochrome P450 2C9 (CYP2C9) variant alleles and the early onset of IPF in the members of this family. VKORC1 (rs9923231 and rs9934438) and CYP2C9 (rs1799853 and rs1057910) were genotyped in this family, which includes a significant number of pulmonary fibrosis patients. In all family members, at least one of the variant alleles tested was present. The presence of the VKORC1 variant alleles in all of the IPF cases and CYP2C9 variants in all but one, which likely leads to a phenotype that is characterized by the early onset and progressive course of IPF. Our findings indicate a role of these allelic variants in (familial) IPF. Therefore, we suggest that the presence of these variants, in association with other pathogenic mutations, should be evaluated during genetic counselling. Our findings might have consequences for the lifestyle of patients with familial IPF in order to prevent the disease from becoming manifest.
Aberrant DOCK2, GRASP, HIF3A and PKFP Hypermethylation has Potential as a Prognostic Biomarker for Prostate Cancer
Authors: Bjerre Marianne T. , Strand Siri H. , Nørgaard Maibritt , Kristensen Helle , Rasmussen Anne KI , Mortensen Martin Mørck , Fredsøe Jacob , Mouritzen Peter , Ulhøi Benedicte , Ørntoft Torben , Borre Michael , Sørensen Karina D.
Published: March 2019

Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, DOCK2, FBXO30, GRASP, HIF3A, MOB3B, PFKP, and TPM4) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75–94%) and specificity (84–100%) for PCa. Furthermore, DOCK2, GRASP, HIF3A and PKFP hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. DOCK2 is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24–3.10), adjusted p = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also.
Curcumin and its Potential for Systemic Targeting of Inflamm-Aging and Metabolic Reprogramming in Cancer
Authors: Kujundžić Renata Novak , Stepanić Višnja , Milković Lidija , Gašparović Ana Čipak , Tomljanović Marko , Trošelj Koraljka Gall
Published: March 2019

Pleiotropic effects of curcumin have been the subject of intensive research. The interest in this molecule for preventive medicine may further increase because of its potential to modulate inflamm-aging. Although direct data related to its effect on inflamm-aging does not exist, there is a strong possibility that its well-known anti-inflammatory properties may be relevant to this phenomenon. Curcumin’s binding to various proteins, which was shown to be dependent on cellular oxidative status, is yet another feature for exploration in depth. Finally, the binding of curcumin to various metabolic enzymes is crucial to curcumin’s interference with powerful metabolic machinery, and can also be crucial for metabolic reprogramming of cancer cells. This review offers a synthesis and functional links that may better explain older data, some observational, in light of the most recent findings on curcumin. Our focus is on its modes of action that have the potential to alleviate specific morbidities of the 21st century.
“Indirect” Information: The Debate on Testimony in Social Epistemology and Its Role in the Game of “Giving and Asking for Reasons”
Authors: Giovagnoli Raffaela
Published: March 2019

We will sketch the debate on testimony in social epistemology by reference to the contemporary debate on reductionism/anti-reductionism, communitarian epistemology and inferentialism. Testimony is a fundamental source of knowledge we share and it is worthy to be considered in the ambit of a dialogical perspective, which requires a description of a formal structure, which entails deontic statuses and deontic attitudes. In particular, we will argue for a social reformulation of the “space of reasons”, which establishes a fruitful relationship with the epistemological view of Wilfrid Sellars.
Matrix-Based Method for Inferring Elements in Data Attributes Using a Vector Space Model
Authors: Hayashi Teruaki , Ohsawa Yukio
Published: March 2019

This article addresses the task of inferring elements in the attributes of data. Extracting data related to our interests is a challenging task. Although data on the web can be accessed through free text queries, it is difficult to obtain results that accurately correspond to user intentions because users might not express their objects of interest using exact terms (variables, outlines of data, etc.) found in the data. In other words, users do not always have sufficient knowledge of the data to formulate an effective query. Hence, we propose a method that enables the type, format, and variable elements to be inferred as attributes of data when a natural language summary of the data is provided as a free text query. To evaluate the proposed method, we used the Data Jacket’s datasets whose metadata is written in natural language. The experimental results indicate that our method outperforms those obtained from string matching and word embedding. Applications based on this study can support users who wish to retrieve or acquire new data.
In Systemic Sclerosis, a Unique Long Non Coding RNA Regulates Genes and Pathways Involved in the Three Main Features of the Disease (Vasculopathy, Fibrosis and Autoimmunity) and in Carcinogenesis
Authors: Dolcino Marzia , Tinazzi Elisa , Puccetti Antonio , Lunardi Claudio
Published: March 2019

Systemic sclerosis (SSc) is an autoimmune disease characterized by three main features: vasculopathy, immune system dysregulation and fibrosis. Long non-coding RNAs (lncRNAs) may play a role in the pathogenesis of autoimmune diseases and a comprehensive analysis of lncRNAs expression in SSc is still lacking. We profiled 542,500 transcripts in peripheral blood mononuclear cells (PBMCs) from 20 SSc patients and 20 healthy donors using Clariom D arrays, confirming the results by Reverse Transcription Polymerase-chain reaction (RT-PCR). A total of 837 coding-genes were modulated in SSc patients, whereas only one lncRNA, heterogeneous nuclear ribonucleoprotein U processed transcript (ncRNA00201), was significantly downregulated. This transcript regulates tumor proliferation and its gene target hnRNPC (Heterogeneous nuclear ribonucleoproteins C) encodes for a SSc-associated auto-antigen. NcRNA00201 targeted micro RNAs (miRNAs) regulating the most highly connected genes in the Protein-Protein interaction (PPI) network of the SSc transcriptome. A total of 26 of these miRNAs targeted genes involved in pathways connected to the three main features of SSc and to cancer development including Epidermal growth factor (EGF) receptor, ErbB1 downstream, Sphingosine 1 phosphate receptor 1 (S1P1), Activin receptor-like kinase 1 (ALK1), Endothelins, Ras homolog family member A (RhoA), Class I Phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase (MAPK), Ras-related C3 botulinum toxin substrate 1 (RAC1), Transforming growth factor (TGF)-beta receptor, Myeloid differentiation primary response 88 (MyD88) and Toll-like receptors (TLRs) pathways. In SSc, the identification of a unique deregulated lncRNA that regulates genes involved in the three main features of the disease and in tumor-associated pathways, provides insight in disease pathogenesis and opens avenues for the design of novel therapeutic strategies.
Sexual Dysfunction and Quality of Life in Chronic Heroin-Dependent Individuals on Methadone Maintenance Treatment
Authors: Llanes Carlos , Álvarez Ana I. , Pastor M. Teresa , Garzón M. Ángeles , González-García Nerea , Montejo Ángel L.
Published: March 2019

This study examined whether methadone (hereinafter referred to as MTD) maintenance treatment (MMT) is correlated with sexual dysfunction (SD) in heroin-dependent men. This was conducted to determine the prevalence of sexual dysfunction and if there is a relationship between duration and dose among men on MMT and its impact on the quality of life. The study combined a retrospective and a cross-sectional survey based on the Kinsey Scale, TECVASP, and PRSexDQ-SALSEX clinical interviews of 85 patients who are currently engaged in MMT. Sexual dysfunction in all five PRSexDQ-SALSEX domains (lack of libido, delay in orgasm, inability to orgasm, erectile dysfunction, and tolerance or acceptance of changes in sexual function) was associated with dose and long-term use of heroin. All dimensions of SD were affected by the MTD intake. From the analysis of our sample, we may conclude that dose of MTD and overall score of SD were directly associated. However, no evidence was found to prove that treatment duration and severity of SD were linked. It is notable that only one tenth of the patients spontaneously reported their symptoms of the sexual sphere, but up to a third considered leaving the MMT for this reason.
Response to Transforaminal Epidural Block as a Useful Predictive Factor of Postherpetic Neuralgia
Authors: Park JungHyun , Baek Su Jin , Baek So Hye , Kim Eung Don
Published: March 2019

Despite the high frequency of nerve blocks in the acute phase of herpes zoster, factors associated with intervention, such as response to epidural block, have not been analyzed as predictive factors of postherpetic neuralgia (PHN). To determine the predictive factors of progression to PHN in the presence of interventions, we analyzed the medical records of 145 patients who underwent transforaminal epidural injection (TFEI) in the acute phase of herpes zoster. A total volume of 5 mL (a mixture of 0.5% lidocaine and 5 mg dexamethasone) was injected during TFEI. Corticosteroid was used only for the first TFEI. Clinical data of age, sex, involved dermatome, presence of comorbidity, time from zoster onset to first TFEI, numerical rating scale (NRS) before TFEI, NRS at 1 week and 1, 3, and 6 months after the first TFEI, and number of TFEI were collected and analyzed. Through multivariate logistic regression analysis, pain improvement less than 50% at 1 week after the first TFEI was a strong predictive factor of progression of PHN at all time points. Response to TFEI appears to be a stronger predictive factor of progression to PHN than patient factors of sex, age, degree of initial pain, and presence of co-morbidity.
Predicting the Epidemiological Dynamics of Lung Cancer in Japan
Authors: Yamaguchi Takayuki , Nishiura Hiroshi
Published: March 2019

While the prevalence of smoking has steadily declined over time, the absolute numbers of lung cancer cases and deaths have continued to increase in Japan. We employed a simple mathematical model that describes the relationship between demographic dynamics and smoking prevalence to predict future epidemiological trends of lung cancer by age and sex. Never-smokers, smokers, and ex-smokers were assumed to experience different hazard of lung cancer, and the model was parameterized using data from 2014 and before, as learning data, and a future forecast was obtained from 2015 onwards. The maximum numbers of lung cancer cases and deaths in men will be 76,978 (95% confidence interval (CI): 76,630–77,253) and 63,284 (95% CI: 62,991–63507) in 2024, while those in women will be 42,838 (95% CI: 42,601–43,095) and 32,267 (95% CI: 32,063–32,460) in 2035 and 2036, respectively. Afterwards, the absolute numbers of cases and deaths are predicted to decrease monotonically. Our compartmental modeling approach is well suited to predicting lung cancer in Japan with dynamic ageing and drastic decline in smoking prevalence. The predicted burden is useful for anticipating demands for diagnosis, treatment, and care in the healthcare sector.
Long-Term Biobanking of Intact Tissue from Lipoaspirate
Authors: Badowski Michael S. , Muise Angela , Harris David T.
Published: March 2019

Autologous fat grafting has now been extensively and successfully performed for more than two decades. Although most adipose grafts and adipose-derived MSC therapies are done with fresh tissue, cryopreservation of tissue allows for much greater flexibility of use. Over the course of five years, 194 cryopreserved adipose samples were thawed and then returned to the collecting physician for subsequent autologous applications. Samples were stored with a mean cryogenic storage time of 9.5 months, with some samples being stored as long as 44 months. The volumes of tissue stored varied from 12 cc to as large as 960 cc. Upon thawing, the volume of recovered whole adipose tissue averaged 67% of the original amount stored for all samples, while the samples that were stored for longer than one year averaged 71%. Recovery was not found to be a function of length of time in cryopreservation. No significant relationship was found between tissue recovery and patient age. While an average recovery of 67% of volume frozen indicates that the use of banked and thawed tissue requires a larger amount of sample to be taken from the patient initially, an experienced clinician easily accomplishes this requirement. As cryopreservation of adipose tissue becomes more commonplace, physicians will find it helpful to know the amount and quality of tissue that will be available after thawing procedures.
Osteochondritis Dissecans (OCD)-Derived Chondrocytes Display Increased Senescence, Oxidative Stress, Chaperone-Mediated Autophagy and, in Co-Culture with Adipose-Derived Stem Cells (ASCs), Enhanced Expression of MMP-13
Authors: Kornicka Katarzyna , Al Naem Mohamad , Röcken Michael , Zmiertka Marta , Marycz Krzysztof
Published: March 2019

Osteochondritis dissecans (OCD) in equids, especially in sport horses, has become a growing issue as it contributes to the occurrence of lameness. Thus the aim of this study was to investigate the cytophysiological properties of OCD chondrocytes including expression of chondrogenic genes, apoptosis, mitochondria dynamics and autophagy. Horse chondrocytes were isolated from healthy (HE) and OCD cartilages. Properties of cells were evaluated using multiple assays e.g., polymerase chain reaction (PCR), immunofluorescence, Western blot. OCD chondrocytes were characterized by increased apoptosis and senescence. Expression of chondrogenic genes (vimentin, aggrecan) was decreased while mRNA levels of matrix metalloproteinase 13 significantly upregulated in comparison to HE cells. Moreover, OCD cells displayed increased mitochondrial fusion while fission events were diminished. Interestingly, chaperone mediated autophagy was triggered in those cells and it predominated over macroautophagy. Furthermore, co-culture of LPS-treated chondrocytes with adipose-derived stem cells (ASC) decreased p62/sequestosome 1 (SQSTM) and increases MMP-13 expression in OCD cells. Our results suggest that OCD affected horse chondrocytes are characterized by senescent phenotype due to endoplasmic reticulum stress and mitochondria dynamics deterioration. Expression of chondrogenic markers is decreased in those cells while expression of chaperone mediated autophagy (CMA)-related genes increased. Increased malfunctioning of cells leads to loss of their functionality and capacity to maintain tissue homeostasis.
Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers
Authors: Kamble Swapnil , Sen Arijit , Dhake Rahul , Joshi Aparna , Midha Divya , Bapat Sharmila
Published: March 2019

Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a pertinent approach in improving prognosis of this highly heterogeneous disease. Enabling the same necessitates identification of class-specific biomarkers and their robust detection in the clinic. We have earlier resolved three discrete molecular HGSC classes associated with distinct functional behavior based on their gene expression patterns, biological networks, and pathways. An important difference revealed was that Class 1 is likely to exhibit cooperative cell migration (CCM), Class 2 undergoes epithelial to mesenchymal transition (EMT), while Class 3 is possibly capable of both modes of migration. In the present study, we define clinical stratification of HGSC tumors through the establishment of standard operating procedures for immunohistochemistry and histochemistry based detection of a panel of biomarkers including TCF21, E-cadherin, PARP1, Slug, AnnexinA2, and hyaluronan. Further development and application of scoring guidelines based on expression of this panel in cell line-derived xenografts, commercial tissue microarrays, and patient tumors led to definitive stratification of samples. Biomarker expression was observed to vary significantly between primary and metastatic tumors suggesting class switching during disease progression. Another interesting feature in the study was of enhanced CCM-marker expression in tumors following disease progression and chemotherapy. These stratification principles and the new information thus generated is the first step towards class-specific personalized therapies in the disease.
Assessment of Sea Level Rise at West Coast of Portugal Mainland and Its Projection for the 21st Century
Authors: Antunes Carlos
Published: March 2019

Based on the updated relative sea level rise rates, 21st-century projections are made for the west coast of Portugal Mainland. The mean sea level from Cascais tide gauge and North Atlantic satellite altimetry data have been analyzed. Through bootstrapping linear regression and polynomial adjustments, mean sea level time series were used to calculate different empirical projections for sea level rise, by estimating the initial velocity and its corresponding acceleration. The results are consistent with an accelerated sea level rise, showing evidence of a faster rise than previous century estimates. Based on different numerical methods of second order polynomial fitting, it is possible to build a set of projection models of relative sea level rise. Applying the same methods to regional sea level anomaly from satellite altimetry, additional projections are also built with good consistency. Both data sets, tide gauge and satellite altimetry data, enabled the development of an ensemble of projection models. The relative sea level rise projections are crucial for national coastal planning and management since extreme sea level scenarios can potentially cause erosion and flooding. Based on absolute vertical velocities obtained by integrating global sea level models, neo-tectonic studies, and permanent Global Positioning System (GPS) station time series, it is possible to transform relative into absolute sea level rise scenarios, and vice-versa, allowing the generation of absolute sea level rise projection curves and its comparison with already established global projections. The sea level rise observed at the Cascais tide gauge has always shown a significant correlation with global sea level rise observations, evidencing relatively low rates of vertical land velocity and residual synoptic regional dynamic effects. An ensemble of sea level projection models for the 21st century is proposed with its corresponding probability density function, both for relative and absolute sea level rise for the west coast of Portugal Mainland. A mean sea level rise of 1.14 m was obtained for the epoch of 2100, with a likely range of 95% of probability between 0.39 m and 1.89 m.
Actions as a Basis for Online Embodied Concepts
Authors: Keily Holly
Published: March 2019

In co-speech gesture research, embodied cognition implies that concepts are associated with haptic and motor information that provides a framework for a gestural plan. When speakers access concepts, embodied action images are automatically activated. This study considers situations in which speakers need to create online concepts of events to investigate the aspect of the event that forms the basis of a new concept. Speakers watched short event video clips with familiar or unfamiliar attributes. They described those clips to partners who had to perform a matching task. Experimental results show that speakers gestured less and produced shorter gestures when relaying longer event descriptions. Speakers were more likely to produce gesture when some aspect of the event was unfamiliar, and they were most sensitive to the familiarity of the event’s main action. Further, when speakers did gesture, they were most likely to gesture to represent the action of the event over the physical attributes of it (the instrument used to enact or the object acted upon). These findings suggest that in creating an embodied concept for something unfamiliar, the motion of the event acts as a basis for their online embodied representation of the concept.
The Effect of Elements of Secondary Structures on the Wear Resistance of Steel in Friction against Experimental Aluminum Alloys for Monometallic Journal Bearings
Authors: Kuznetsova Ekaterina , Gershman Iosif , Mironov Alexander , Podrabinnik Pavel , Peretyagin Pavel
Published: March 2019

This article describes the elemental composition of secondary structures formed on the steel contact surface during wear test against experimental Al alloys. Wear tests were carried out according to the rotating steel roller-fixed shoe of an antifriction alloy scheme under boundary lubrication conditions. The duration of the test was 40 h, and motor oil M14V2 was used as a lubricant. The microstructure and elemental characterization of the steel surface before and after the tribological test was obtained by scanning electron microscopy equipped with EDX. The simultaneous presence of various constituents of oil, steel, and Al alloys can produce both positive and negative effects on the friction characteristic of the tribosystem. It was shown that presence of Mo, F, S, Si, Ni, and Cr have a favorable effect on the wear resistance of steel and the friction coefficient of the rubbing surfaces due to the formation of secondary structures with optimal composition.
Evaluation Based on Distance from Average Solution Method for Multiple Criteria Group Decision Making under Picture 2-Tuple Linguistic Environment
Authors: Zhang Siqi , Gao Hui , Wei Guiwu , Wei Yu , Wei Cun
Published: March 2019

In this paper, we design the EDAS (evaluation based on distance from average solution) model with picture 2-tuple linguistic numbers (P2TLNs). First, we briefly reviewed the definition of P2TLSs and introduced the score function, accuracy function, and operational laws of P2TLNs. Then, we combined the traditional EDAS model for multiple criteria group decision making (MCGDM) with P2TLNs. Our presented model was more accurate and effective for considering the conflicting attributes. Finally, a numerical case for green supplier selection was given to illustrate this new model, and some comparisons were also conducted between the picture 2-tuple linguistic weighted averaging (P2TLWA), picture 2-tuple linguistic weighted geometric (P2TLWG) aggregation operators and EDAS model with P2TLNs, to further illustrate the advantages of the new method.
Mechanical Behavior of Inconel 625 at Elevated Temperatures
Authors: de Oliveira Mauro M. , Couto Antônio A. , Almeida Gisele F. C. , Reis Danieli A. P. , de Lima Nelson B. , Baldan Renato
Published: March 2019

Inconel 625 is a nickel-based alloy that is mainly used in high-temperature applications. Inconel 625 exhibits an unstable plastic flow at elevated temperatures characterized by serrated yielding, well-known as the Portevin-Le Chatelier effect. The evaluation of the mechanical properties of Inconel 625 at high temperatures is the aim of this work. The tensile tests were executed in temperatures ranging from room temperature to 1000 °C with strain rates of 2 × 10−4 to 2 × 10−3 s−1. The creep tests were executed in the temperature range of 600–700 °C and in the stress range of 500–600 MPa in a constant load mode. The optical and scanning electron microscopes were used for surface fracture observation. In the curves obtained at 200–700 °C the serrated stress-strain behavior was observed, which was related to the dynamic strain aging effect. The yield strength and the elongation values show anomalous behavior as a function of the test temperature. An intergranular cracking was observed for a specimen tensile tested at 500 °C that can be attributed to the decohesion of the carbides along the grain boundaries. The fracture surface of the specimen tensile tested at 700 °C showed the predominance of transgranular cracking with tear dimples with a parabolic shape.
Model Development for Refining Rates in Oxygen Steelmaking: Impact and Slag-Metal Bulk Zones
Authors: Kadrolkar Ameya , Dogan Neslihan
Published: March 2019

A new approach has been adopted to predict the contribution of the impact and slag-metal bulk zones to the refining rates of impurities in a top blown oxygen steelmaking process. The knowledge pertaining to the behavior of top-jets and bottom stirring plumes (water model and industrial studies) was adapted. For the impact zone, the surface renewal generated by the top jet as well as bottom stirring plumes is incorporated in the current model, whereas in the case of slag-metal bulk zones the surface renewal is caused solely by the bottom stirring plumes. This approach helped in achieving a more explicit use of process parameters in quantifying the slag formation. The results suggest a minor contribution of these two zones to the overall refining of impurities throughout the oxygen blow.
Modeling Electrical Resistivity of Naturally Aged Al–Mg–Si Alloys
Authors: Bahrami Abbas , Yazdan Mehr Maryam
Published: March 2019

Isothermal ageing of Al–Mg–Si alloys, stored at room temperature for more than 5 months, is associated with an unexpected significant increase in the overall electrical resistivity. This unexpected anomalous increase is not observed in alloys with shorter storage (natural ageing) times. This phenomenon is explained with a scenario, based on the evolution of the size distribution of Guinier–Preston (GP) zones during natural ageing and during subsequent artificial ageing. The proposed scenario can explain the contribution of natural ageing atomic clusters to this anomalous increase in the electrical resistivity. A physically based combined precipitation–electrical resistivity model, with the former being based on simultaneous nucleation-growth-coarsening reactions and the latter based on the Bragg scattering of electrons from atomic clusters, has been used to explain the electrical resistivity evolution. It is shown that the proposed model is capable of reproducing the experimental data in both short natural ageing (less than 5 months) and long natural ageing (more than 5 months) regimes.
Chemical Evolution of Nb-Ta Oxides and Cassiterite in Phosphorus-Rich Albite-Spodumene Pegmatites in the Kangxiwa–Dahongliutan Pegmatite Field, Western Kunlun Orogen, China
Authors: Feng Yonggang , Liang Ting , Yang Xiuqing , Zhang Ze , Wang Yiqian
Published: March 2019

The Kangxiwa–Dahongliutan pegmatite field in the Western Kunlun Orogen, China contains numerous granitic pegmatites around a large granitic pluton (the Dahongliutan Granite with an age of ca. 220 to 217 Ma), mainly including barren garnet-, tourmaline-bearing pegmatites, Be-rich beryl-muscovite pegmatites, and Li-, P-rich albite-spodumene pegmatites. The textures, major element contents, and trace element concentrations of columbite-group minerals (CGM) and cassiterite from three albite-spodumene pegmatites in the region were investigated using a combination of optical microscopy, SEM, EPMA and LA-ICP-MS. The CGM can be broadly classified into four types: (1) inclusions in cassiterite; (2) euhedral to subhedral crystals (commonly exhibiting oscillatory and/or sector zoning and coexisting with magmatic cassiterite); (3) anhedral aggregates; (4) tantalite-(Fe)-ferrowodginite (FeSnTa2O8) intergrowths. The compositional variations of CGM and cassiterite are investigated on the mineral scale, in individual pegmatites and within the pegmatite group. The evolution of the pegmatites is also discussed. The variation of Nb/Ta and Zr/Hf ratios of the cassiterite mimics the Nb-Ta and Zr-Hf fractionation trends in many LCT pegmatites, indicating that these two ratios of cassiterite may bear meanings regarding the pegmatite evolution.
Multi-Spheres Adsorptive Microextraction (MSAμE)—Application of a Novel Analytical Approach for Monitoring Chemical Anthropogenic Markers in Environmental Water Matrices
Authors: Silva Ana R. M. , Neng Nuno R. , Nogueira José M. F.
Published: March 2019

Multi-spheres adsorptive microextraction using powdered activated carbons (ACs) was studied as a novel enrichment approach, followed by liquid desorption and high-performance liquid chromatography with diode array detection (MSAµE(AC)-LD/HPLC-DAD) to monitor caffeine (CAF) and acetaminophen (ACF) traces in environmental matrices. In this study, commercial activated carbons (N, NOX, and R) were tested, with the latter showing a much better performance for the analysis of both anthropogenic drugs. The main parameters affecting the efficiency of the proposed methodology are fully discussed using commercial AC(R). Textural and surface chemistry properties of the ACs sample were correlated with the analytical results. Assays performed on 30 mL of water samples spiked at 10 µg L−1 under optimized experimental conditions, yielding recoveries of 75.3% for ACF and 82.6% for CAF. The methodology also showed excellent linear dynamic ranges for both drugs with determination coefficients higher than 0.9976, limits of detection and quantification of 0.8–1.2 µg L−1 and 2.8–4.0 µg L−1, respectively, and suitable precision (RSD < 13.8%). By using the standard addition method, the application of the present method to environmental matrices, including superficial, sea, and wastewater samples, allowed very good performance at the trace level. The proposed methodology proved to be a feasible alternative for polar compound analysis, showing to be easy to implement, reliable, and sensitive, with the possibility to reuse and store the analytical devices loaded with the target compounds for later analysis.
In Silico Methods for the Discovery of Orthosteric GABAB Receptor Compounds
Authors: Evenseth Linn M. , Warszycki Dawid , Bojarski Andrzej J. , Gabrielsen Mari , Sylte Ingebrigt
Published: March 2019

The GABAB receptor (GABAB-R) is a heterodimeric class C G protein-coupled receptor comprised of the GABAB1a/b and GABAB2 subunits. The endogenous orthosteric agonist γ-amino-butyric acid (GABA) binds within the extracellular Venus flytrap (VFT) domain of the GABAB1a/b subunit. The receptor is associated with numerous neurological and neuropsychiatric disorders including learning and memory deficits, depression and anxiety, addiction and epilepsy, and is an interesting target for new drug development. Ligand- and structure-based virtual screening (VS) are used to identify hits in preclinical drug discovery. In the present study, we have evaluated classical ligand-based in silico methods, fingerprinting and pharmacophore mapping and structure-based in silico methods, structure-based pharmacophores, docking and scoring, and linear interaction approximation (LIA) for their aptitude to identify orthosteric GABAB-R compounds. Our results show that the limited number of active compounds and their high structural similarity complicate the use of ligand-based methods. However, by combining ligand-based methods with different structure-based methods active compounds were identified in front of DUDE-E decoys and the number of false positives was reduced, indicating that novel orthosteric GABAB-R compounds may be identified by a combination of ligand-based and structure-based in silico methods.
Acute Administration of Desformylflustrabromine Relieves Chemically Induced Pain in CD-1 Mice
Authors: Weggel Loni A. , Pandya Anshul A.
Published: March 2019

Neuronal nicotinic acetylcholine receptors are cell membrane-bound ion channels that are widely distributed in the central nervous system. The α4β2 subtype of neuronal nicotinic acetylcholine receptor plays an important role in modulating the signaling pathways for pain. Previous studies have shown that agonists, partial agonists, and positive allosteric modulators for the α4β2 receptors are effective in relieving pain. Desformylflustrabromine is a compound that acts as an allosteric modulator of α4β2 receptors. The aim of this study was to assess the effects of desformylflustrabromine on chemically induced pain. For this purpose, the formalin-induced pain test and the acetic acid-induced writhing response test were carried out in CD-1 mice. Both tests represent chemical assays for nociception. The results show that desformylflustrabromine is effective in producing an analgesic effect in both tests used for assessing nociception. These results suggest that desformylflustrabromine has the potential to become a clinically used drug for pain relief.
A New Generation of Minor-Groove-Binding—Heterocyclic Diamidines That Recognize G·C Base Pairs in an AT Sequence Context
Authors: Paul Ananya , Guo Pu , Boykin David W. , Wilson W. David
Published: March 2019

We review the preparation of new compounds with good solution and cell uptake properties that can selectively recognize mixed A·T and G·C bp sequences of DNA. Our underlying aim is to show that these new compounds provide important new biotechnology reagents as well as a new class of therapeutic candidates with better properties and development potential than other currently available agents. In this review, entirely different ways to recognize mixed sequences of DNA by modifying AT selective heterocyclic cations are described. To selectively recognize a G·C base pair an H-bond acceptor must be incorporated with AT recognizing groups as with netropsin. We have used pyridine, azabenzimidazole and thiophene-N-methylbenzimidazole GC recognition units in modules crafted with both rational design and empirical optimization. These modules can selectively and strongly recognize a single G·C base pair in an AT sequence context. In some cases, a relatively simple change in substituents can convert a heterocyclic module from AT to GC recognition selectivity. Synthesis and DNA interaction results for initial example lead modules are described for single G·C base pair recognition compounds. The review concludes with a description of the initial efforts to prepare larger compounds to recognize sequences of DNA with more than one G·C base pairs. The challenges and initial successes are described along with future directions.
Bimodal Fucoidan-Coated Zinc Oxide/Iron Oxide-Based Nanoparticles for the Imaging of Atherothrombosis
Authors: Nguyen Hoang , Tinet Eric , Chauveau Thierry , Geinguenaud Frédéric , Lalatonne Yoann , Michel Aude , Aid-Launais Rachida , Journé Clément , Lefèbvre Caroline , Simon-Yarza Teresa , Motte Laurence , Jouini Noureddine , Tualle Jean-Michel , Chaubet Frédéric
Published: March 2019

A polyol method was used to obtain ultrasmall ZnO nanoparticles (NPs) doped with iron ions and coated with a low molecular weight fucoidan in order to perform in vivo MR and ex vivo fluorescence imaging of athrothrombosis. During the synthesis, the early elimination of water by azeotropic distillation with toluene allowed us to produce NPs which size, determined by XRD and TEM, decreased from 7 nm to 4 nm with the increase of iron/zinc ratios from 0.05 to 0.50 respectively. For the highest iron content (NP-0.50) NPs were evidenced as a mixture of nanocrystals made of wurtzite and cubic phase with a molar ratio of 2.57:1, although it was not possible to distinguish one from the other by TEM. NP-0.50 were superparamagnetic and exhibited a large emission spectrum at 470 nm when excited at 370 nm. After surface functionalization of NP-0.50 with fucoidan (fuco-0.50), the hydrodynamic size in the physiological medium was 162.0 ± 0.4 nm, with a corresponding negative zeta potential of −48.7 ± 0.4 mV, respectively. The coating was evidenced by FT-IR spectra and thermogravimetric analysis. Aqueous suspensions of fuco-0.50 revealed high transverse proton relaxivities (T2) with an r2 value of 173.5 mM−1 s−1 (300 K, 7.0 T) and remained stable for more than 3 months in water or in phosphate buffer saline without evolution of the hydrodynamic size and size distribution. No cytotoxic effect was observed on human endothelial cells up to 48 h with these NPs at a dose of 0.1 mg/mL. After injection into a rat model of atherothrombosis, MR imaging allowed the localization of diseased areas and the subsequent fluorescence imaging of thrombus on tissue slices.
Synthesis of Carbon Quantum Dot Nanoparticles Derived from Byproducts in Bio-Refinery Process for Cell Imaging and In Vivo Bioimaging
Authors: Huang Caoxing , Dong Huiling , Su Yan , Wu Yan , Narron Robert , Yong Qiang
Published: March 2019

The carbon quantum dot (CQD), a fluorescent carbon nanoparticle, has attracted considerable interest due to its photoluminescent property and promising applications in cell imaging and bioimaging. In this work, biocompatible, photostable, and sustainably sourced CQDs were synthesized from byproducts derived from a biorefinery process using one-pot hydrothermal treatment. The main components of byproducts were the degradation products (autohydrolyzate) of biomass pretreated by autohydrolysis. The as-synthesized CQDs had a size distribution from 2.0–6.0 nm and had high percentage of sp2 and sp3 carbon groups. The CQDs showed blue-green fluorescence with a quantum yield of ~13%, and the fluorescence behaviors were found to be stable with strong resistance to photobleaching and temperature change. In addition, it is found that the as-synthesized CQDs could be used for imaging of cells and tumors, which show potential applications in bioimaging and related fields such as phototherapy and imaging.
Full Counting Statistics of Electrons through Interaction of the Single Quantum Dot System with the Optical Field
Authors: Liu Weici , Wang Faqiang , Tang Zhilie , Liang Ruisheng
Published: March 2019

In this paper, using the particle-number-resolved master equation, the properties of full counting statistics (FCS) are investigated for a single quantum dot (QD) system interacting with optical fields in the thermal state, Fock state, coherent state, and coherent state with random phase. In these diverse quantum states of optical fields, average tunneling currents have different step shoulder heights at a lower bias voltage with the same light intensity, and a staircase-shaped current can be induced unexpectedly in vacuum state optical field. The characteristics of the Fano factor and skewness in the coherent state differ from those in all of the other cases. For avalanche-like transport at a lower bias voltage, the mechanism is a dynamical channel blockade in a moderate electron–photon interaction regime. There is a pronounced negative differential conductance that results from tuning the phase of the coherent state optical field in a symmetric QD system.
Recent Progress on Graphene-Functionalized Metasurfaces for Tunable Phase and Polarization Control
Authors: Cheng Jierong , Fan Fei , Chang Shengjiang
Published: March 2019

The combination of graphene and a metasurface holds great promise for dynamic manipulation of the electromagnetic wave from low terahertz to mid-infrared. The optical response of graphene is significantly enhanced by the highly-localized fields in the meta-atoms, and the characteristics of meta-atoms can in turn be modulated in a large dynamic range through electrical doping of graphene. Graphene metasurfaces are initially focused on intensity modulation as modulators and tunable absorbers. In this paper, we review the recent progress of graphene metasurfaces for active control of the phase and the polarization. The related applications involve, but are not limited to lenses with tunable intensity or focal length, dynamic beam scanning, wave plates with tunable frequency, switchable polarizers, and real-time generation of an arbitrary polarization state, all by tuning the gate voltage of graphene. The review is concluded with a discussion of the existing challenges and the personal perspective of future directions.
Hypertension Associated with Fructose and High Salt: Renal and Sympathetic Mechanisms
Authors: Komnenov Dragana , Levanovich Peter E. , Rossi Noreen F.
Published: March 2019

Hypertension is a leading cause of cardiovascular and chronic renal disease. Despite multiple important strides that have been made in our understanding of the etiology of hypertension, the mechanisms remain complex due to multiple factors, including the environment, heredity and diet. This review focuses on dietary contributions, providing evidence for the involvement of elevated fructose and salt consumption that parallels the increased incidence of hypertension worldwide. High fructose loads potentiate salt reabsorption by the kidney, leading to elevation in blood pressure. Several transporters, such as NHE3 and PAT1 are modulated in this milieu and play a crucial role in salt-sensitivity. High fructose ingestion also modulates the renin-angiotensin-aldosterone system. Recent attention has been shifted towards the contribution of the sympathetic nervous system, as clinical trials demonstrated significant reductions in blood pressure following renal sympathetic nerve ablation. New preclinical data demonstrates the activation of the renal sympathetic nerves in fructose-induced salt-sensitive hypertension, and reductions of blood pressure after renal nerve ablation. This review further demonstrates the interplay between sodium handling by the kidney, the renin-angiotensin-aldosterone system, and activation of the renal sympathetic nerves as important mechanisms in fructose and salt-induced hypertension.
Is A Healthy Diet Associated with Lower Anthropometric and Glycemic Alterations in Predisposed Children Born from Mothers with Gestational Diabetes Mellitus?
Authors: Dugas Camille , Bélanger Mélissa , Perron Julie , Weisnagel S. John , Tchernof André , Marc Isabelle , Robitaille Julie
Published: March 2019

Children born from mothers with gestational diabetes mellitus (GDM) are at high-risk of obesity and type 2 diabetes. To date, there is a lack of effective strategies to prevent these complications. The aim of this study was to evaluate the association between diet quality and anthropometric and glycemic profiles of children exposed (GDM+) and unexposed (GDM–) to GDM. A total of 104 GDM+ and 38 GDM– children were included. Two 24-h dietary recall questionnaires were used to assess dietary intakes. The Healthy Eating Index adapted for the Canadian population (HEI-C) was used to assess diet quality. Spearman correlations adjusted for children’s age and sex were computed. Mean age was 6.0 ± 2.5 and 6.8 ± 2.3 years for GDM+ and GDM–, respectively (p = 0.03). Total HEI-C score was negatively associated with the android-to-gynoid fat mass ratio (r = −0.29, p = 0.03) and homeostasis model assessment for insulin resistance (HOMA-IR) index (r = −0.22, p = 0.04) in GDM+ children only. The prevalence of being overweight or obese during childhood was 4-fold higher among GDM+ children with a HEI-C score ≤70 compared to GDM+ children with a HEI-C score >70. Results of this study show that a healthy diet is associated with a better cardiometabolic health profile in GDM+ children, including a lower risk of being overweight or obese.