bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism and Diastereoselectivity of [3+3] Cycloaddition between Enol Diazoacetate and Azomethine Imine Catalyzed by Dirhodium Tetracarboxylate: A Theoretical Study
Authors: Zhang Yan , Yang Yongsheng , Zhao Jianming , Xue Ying
Published: April 2018

The mechanism and diastereoselectivity of the dirhodium‐catalyzed [3+3] cycloaddition reaction between an enol diazoacetate and an azomethine imine in toluene to produce bicyclic pyrazolidinone derivatives have been investigated by DFT at the M06‐GD3/6‐311+G(2d,2p) [Rh‐RSC+4f]//M06‐GD3/6‐31G(d,p) [Rh‐RSC+4f] level combined with the solvation SMD model. The results revealed that the reaction process, beginning with the rhodium–carbene active intermediate, occurs in two steps: Vinylogous addition (C–N bond forming) and intramolecular six‐numbered ring closure (C–C bond forming), with the second step being rate‐limiting. Furthermore, the origin of the diastereoselectivity was investigated by orbital composition analysis, distortion/interaction analysis, and natural bond orbital calculations and found to be a result of steric and electronic effects.
Organic selenium, selenate, and selenite accumulation by lake plankton and the alga Chlamydomonas reinhardtii at different pH and sulfate concentrations
Authors: Ponton Dominic E. , Fortin Claude , Hare Landis
Published: April 2018

Selenium (Se) concentrations measured in lake planktonic food chains (microplankton <64 μm, copepods, and Chaoborus larvae) were strongly correlated with the concentrations of dissolved organic Se. These correlations were strengthened slightly by adding the concentrations of dissolved selenate to those of organic Se. To better understand the role of Se species and the influence of water chemistry on Se uptake, we exposed the green alga Chlamydomonas reinhardtii to selenite, selenate, or selenomethionine at various H+ ion and sulfate concentrations under controlled laboratory conditions. At low sulfate concentrations, inorganic Se species (selenate >> selenite) were more readily accumulated by this alga than was selenomethionine. However, at higher sulfate concentrations the uptake of selenite was higher than that of selenate, whereas the uptake of selenomethionine remained unchanged. Although the pH of the exposure water did not influence the uptake of selenate by this alga, the accumulation of selenomethionine and selenite increased with pH because of their relative pH-related speciation. The Se concentrations that we measured in C. reinhardtii exposed to selenomethionine were 30 times lower than those that we measured in field-collected microplankton exposed in the same laboratory conditions. This difference is explained by the taxa present in the microplankton samples. Using the present laboratory measurements of Se uptake in microplankton and of natural Se concentrations in lake water allowed us to model Se concentrations in a lake pelagic food chain. Environ Toxicol Chem 2018;37:2112–2122. © 2018 SETAC
Choosing IoT‐connectivity? A guiding methodology based on functional characteristics and economic considerations
Authors: Vannieuwenborg Frederic , Verbrugge Sofie , Colle Didier
Published: April 2018

Along with the growing market of Internet of Things (IoT), the set of IoT‐connectivity networks is also continuously expanding. Large‐scale deployments of the new low‐power wide‐area networks and announcements of new technologies prove this trend. Although these new technologies take care of some key IoT‐challenges, such as communication cost and power consumption, careful consideration of the IoT‐connectivity is still required since there is no one‐size‐fits‐all solution. Typical comparisons of IoT‐connectivity networks are based on technical characteristics but remain unpractical when it comes down to comparing functional characteristics. Questions on public network accessibility, ability for private network deployments, and cost considerations related to IoT‐connectivity networks often remain unanswered. In this work, a 2‐step methodology is proposed to guide IoT‐developers in choosing an appropriate connectivity network. First, a questionnaire walkthrough eliminates IoT‐connectivity networks based on mismatches between their functional characteristics and the functional requirements of the IoT‐applications. In a second step, an evaluation of the main cost components related to IoT‐connectivity indicates the most economical solution. As an illustration, we present 2 case studies: (1) deploying smart shipping containers in the port of Antwerp and (2) installing shop'n go parking spaces, which detect vehicle presence via a sensor.
The path toward a cloud‐aware mobile network protocol stack
Authors: Serrano Pablo , Gramaglia Marco , Bega Dario , Gutierrez‐Estevez David , Garcia‐Aviles Gines , Banchs Albert
Published: April 2018

We are currently observing the softwarization of communication networks, where network functions are translated from monolithic pieces of equipment to programs running over a shared pool of computational, storage, and communication resources. While it is clear that almost any softwarization improves flexibility (eg, the ability to instantiate more servers to cope with increasing traffic demand), in this paper, we advocate for a complete redesign of the communications protocol stack, instead of a mere translation of hardware functions into software. We discuss 2 drivers for this cloud‐aware redesign: (1) relaxing the tight interactions between functions and (2) supporting a graceful degradation of the service when resources become scarce. The potential benefits of this redesign are illustrated with the numerical evaluation of one use case.
Exploration of Complex Electrochemical and Chemo‐mechanical Behavior of Solid Oxide Fuel Cell Fueled with Pyrolysis Bio‐oil
Authors: Elleuch A. , Halouani K. , Li Y.
Published: April 2018

Direct utilization of olive mill wastewater sludge (OMWS) bio‐oil preparedviafast pyrolysis in a Direct‐Biofuel Solid Oxide Fuel Cell (DB‐SOFC) was investigated. A viable power densities (>1,000 W m−2at 650 °C) and 6 h operation under open circuit conditions were obtained despite crude bio‐oil complex chemistry. When heated, bio‐oil decomposes yielding gases, volatiles and solid residues (biochar). At 650 °C, polarization curve and impedance spectra of SOFC fed by bio‐oil showed peculiar shapes related to complex kinetics and charge transfer mechanism within the anode. The carbon accumulation at 650 °C is managed through oxidations with oxide ions and chemical reaction with CO2and H2O gases. Above 700 °C, performance degradation was noted related to biochar accumulation at the anode though the promotion of Boudouard reaction, the increase in O2−transfer and possible carbon electrochemical oxidations. The anode chemo‐mechanical instability was observed explaining the rise in cell ohmic resistance and performance degradation after 6 operating hours. Globally, this work demonstrates that direct fed SOFCs with OMWS bio‐oil is achievable using Ni‐SDC anode but enhancement in fuel quality and in anode catalytic activity and stability are required to improve significantly the cell performance.
Integrated Environmental Planning and Permitting Enables Project Success
Authors: Latimer Shane
Published: April 2018

It is clear, sometimes painfully so, to anyone experienced with siting new utility infrastructure that environmental planning and permitting is often a complex undertaking. This article provides guidance to help smooth the process and keep your project on time and on budget.
Effects ofSYN1Q555Xmutation on cortical gray matter microstructure
Authors: Cabana Jean‐François , Gilbert Guillaume , Létourneau‐Guillon Laurent , Safi Dima , Rouleau Isabelle , Cossette Patrick , Nguyen Dang Khoa
Published: April 2018

A newQ555Xmutation on theSYN1gene was recently found in several members of a family segregating dyslexia, epilepsy, and autism spectrum disorder. To describe the effects of this mutation on cortical gray matter microstructure, we performed a surface‐based group study using novel diffusion and quantitative multiparametric imaging on 13SYN1Q555Xmutation carriers and 13 age‐ and sex‐matched controls. Specifically, diffusion kurtosis imaging (DKI) and neurite orientation and dispersion and density imaging (NODDI) were used to analyze multi‐shell diffusion data and obtain parametric maps sensitive to tissue structure, while quantitative metrics sensitive to tissue composition (T1, T2* and relative proton density [PD]) were obtained from a multi‐echo variable flip angle FLASH acquisition. Results showed significant microstructural alterations in several regions usually involved in oral and written language as well as dyslexia. The most significant changes in these regions were lowered mean diffusivity and increased fractional anisotropy. This study is, to our knowledge, the first to successfully use diffusion imaging and multiparametric mapping to detect cortical anomalies in a group of subjects with a well‐defined genotype linked to language impairments, epilepsy and autism spectrum disorder (ASD).
De Novo Hepatocellular Carcinoma Among Liver Transplant Registrants in the Direct Acting Antiviral Era
Authors: Kwong Allison J. , Kim W. Ray , Flemming Jennifer A.
Published: April 2018

The risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) receiving direct acting antivirals (DAAs) has been debated. This study aims to describe the incidence of HCC among patients listed for liver transplantation (LT) in the DAA era. Individuals with cirrhosis listed for LT from January 2003 to December 2015 were identified using the Scientific Registry for Transplant Recipients database. Patients with HCC at listing or HCC exception within 180 days were excluded. Patients were divided into three eras based on listing date: eras 1 (2003‐2010), 2 (2011‐2013), and 3 (2014‐2015). Incidence rates of HCC were calculated by era and compared using incident rate ratios (IRRs). The association between HCC and listing era was evaluated using Cox regression and competing risk analyses, the latter considering death and LT as competing events. Of the 48,158 eligible wait‐list registrants, 3112 (6.5%) received HCC exceptions after a median of 493 days. In 20,039 individuals with HCV, the incidence of HCC was 49% higher in era 3 versus era 1 (IRR 1.49, 95% confidence interval [CI] 1.24‐1.79). In multivariate analysis, those in era 3 had a higher hazard of HCC compared with era 1 (hazard ratio 1.22, 95% CI 1.01‐1.48). However, in multivariable competing risks analysis, with death and LT considered as competing events for de novo HCC, era was no longer associated with HCC (subdistribution hazard ratio 0.83, 95% CI 0.69‐1.00). Conclusion: In this large population‐based cohort of LT registrants, the incidence of HCC among HCV patients has increased in the DAA era. Competing risks analysis suggests that this may be explained by changes in rates of LT and wait‐list mortality in the HCV population during this time. (Hepatology 2018; 00:000‐000).
Use of depth of response to predict progression‐free survival in relapsed or refractory multiple myeloma: Evaluation of results from 102 clinical trials
Authors: Mangal Naveen , Salem Ahmed Hamed , Menon Rajeev M. , Freise Kevin J.
Published: April 2018

Progression‐free survival (PFS) is the standard endpoint for demonstration of clinical effectiveness of novel therapies in relapsed or refractory multiple myeloma (RRMM). However, the long evaluation times for PFS limits its usefulness in the development of new therapies. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in RRMM. A database was systematically developed from 268 identified RRMM trials reported from 1999 to 2016. Evaluated covariates for the relationship between response rates and PFS included age, sex, drug class(es), and number of drug classes. One‐hundred two (102) trials involving 136 cohorts were included in the meta‐analysis, representing 13 322 patients in total. Regression analysis using response rates and median PFS indicated that the correlation between very good partial response (VGPR) or better and median PFS was higher (R2 = 0.63) than the separately analyzed correlations between clinical benefit, overall response, or complete response rate and median PFS (R2 = 0.47 – 0.52). Subsequent covariate analysis revealed that treatment with an immunomodulatory imide drug (IMiD) further improved the relationship (R2 = 0.69), with a longer median PFS at a given VGPR or better rate when at least 1 drug treatment was an IMiD. Number of drug classes was not found to alter this relationship. In conclusion, VGPR or better rate can be used to predict the median PFS, with adjustment for the additional PFS provided by an IMiD.
A numerical study on the occurrence of flowing wells in the discharge area of basins due to the upward hydraulic gradient induced wellbore flow
Authors: Zhang Zhi‐Yuan , Jiang Xiao‐Wei , Wang Xu‐Sheng , Wan Li , Wang Jun‐Zhi
Published: April 2018

The occurrence of flowing wells in basins has been found to be closely related to the discharge area with an upward hydraulic gradient. Unfortunately, previous studies on upward gradient induced wellbore flow with equaling total inflow (Qin) in the deep and total outflow (Qout) in the shallow could not explain the occurrence of flowing wells. By representing wells using the MNW2 Package imbedded in MODFLOW 2005, we obtain the exchange of groundwater between the aquifer and the well in the discharge area of 3D unit basins and identify three scenarios: Qin = Qout, Qin > Qout > 0 and Qin > Qout = 0. The relationship of Qin > Qout well explains why flowing wells only develop in a limited part of the discharge area. Sensitivity analysis shows that well location, water table undulation, and basin length–depth ratio do not change the profile of the ratio of cumulative flow rate in a flowing well to total inflow (Qv/Qin) versus the relative elevation in the inflow segment, zin*, but could significantly change the length of the inflow segment; well depth could change both the length of the inflow segment and the profile of Qv/Qin versus zin*. Based on the numerical results in homogeneous and isotropic basins with different basin length–depth ratios in the current study, the ratio of inflow in the lower half part of a flowing well to the total inflow is found to be at least 67% and could be close to 100%, indicating that water at the outlets of flowing wells with long open sections is mainly from the deep part of the well.
Chemostatic behaviour of major ions and contaminants in a semiarid spring and stream system near Los Alamos, NM, USA
Authors: Koger Jace M. , Newman Brent D. , Goering Timothy J.
Published: April 2018

Recent studies have focused on the relationship between solute concentrations and discharge in streams, demonstrating that concentrations can vary little relative to changes in discharge (chemostatic behaviour). Chemostatic behaviour is dependent on catchment characteristics (e.g., lithology, geomorphology, and vegetation) and chemical characteristics of the solute (e.g., availability, reactivity, and mobility). An investigation of 3 springs and a stream near Los Alamos, NM, reveals that springs can behave in a chemostatic fashion as stream systems tend to do. Another unique finding of this study is that the anthropogenic contaminants barium and the high explosive RDX (hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine) can also behave chemostatically. The chemostatic behaviour of a contaminant has important implications for the residence time of contaminants in a system as well as having a major control on contaminant flux and mass transport. Redox (reduction–oxidation) and biogeochemically sensitive analytes (e.g., Fe, SO4, and NO3) display a combination of chemostatic and chemodynamic behaviour, showing the influence of temporally variable conditions on stream and spring chemistries.
Children's psycho‐spatial understanding of affect‐based time: The developmental trajectories of ego‐ and event‐moving perspectives
Authors: McAfee Ciara A. , Wyckoff Emily P. , Choe Katherine S.
Published: April 2018

Time is closely linked to people's representation of spatial experience. Previous research showed that adults primed with positive affect judged that they were approaching the event (ego‐moving), whereas those primed with negative affect reported that the event was approaching them (event‐moving). The present research investigated the developmental sensitivity towards psycho‐spatial understanding by examining the role of positive and negative affect on children's perception of time. In Study 1, when tested in a within‐subjects design, 5‐, 7‐, and 9‐year‐olds as well as adults made ego‐moving judgments in response to an object of the positive event that was to happen in 2 days. However, by 9 years, children made adult‐like event‐moving responses to an object that stood for the negative affect. Five‐year‐olds continued to make ego‐moving judgments in the negative valence condition, whereas 7‐year‐olds' responses were in transition. Study 2 replicated the full developmental pattern found in Study 1, even when the positive and negative affect events were towards the identical object in the between‐subjects design and the time span was shortened to a few minutes. Implications of the affective spatiotemporal perception of time were further discussed in relation to the sense of agency.

Highlights

We uncover the pattern of developmental sensitivity towards the psycho‐spatial embodiment of time, in relation to a positive or negative event.

Vignettes were used to ascertain participant's psycho‐spatial view of time in relation to valence; 9‐year‐olds had an adult‐like understanding.

Teaching children to use different psycho‐spatial agentic perspectives has the potential to help children at risk of anxiety and depression.
Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer
Authors: Diquigiovanni Chiara , Bergamini Christian , Evangelisti Cecilia , Isidori Federica , Vettori Andrea , Tiso Natascia , Argenton Francesco , Costanzini Anna , Iommarini Luisa , Anbunathan Hima , Pagotto Uberto , Repaci Andrea , Babbi Giulia , Casadio Rita , Lenaz Giorgio , Rhoden Kerry J. , Porcelli Anna Maria , Fato Romana , Bowcock Anne , Seri Marco , Romeo Giovanni , Bonora Elena
Published: April 2018

Familial aggregation is a significant risk factor for the development of thyroid cancer and familial non‐medullary thyroid cancer (FNMTC) accounts for 5–7% of all NMTC. Whole exome sequencing analysis in the family affected by FNMTC with oncocytic features where our group previously identified a predisposing locus on chromosome 19p13.2, revealed a novel heterozygous mutation (c.400G > A, NM_012335; p.Gly134Ser) in exon 5 of MYO1F, mapping to the linkage locus. In the thyroid FRTL‐5 cell model stably expressing the mutant MYO1F p.Gly134Ser protein, we observed an altered mitochondrial network, with increased mitochondrial mass and a significant increase in both intracellular and extracellular reactive oxygen species, compared to cells expressing the wild‐type (wt) protein or carrying the empty vector. The mutation conferred a significant advantage in colony formation, invasion and anchorage‐independent growth. These data were corroborated by in vivo studies in zebrafish, since we demonstrated that the mutant MYO1F p.Gly134Ser, when overexpressed, can induce proliferation in whole vertebrate embryos, compared to the wt one. MYO1F screening in additional 192 FNMTC families identified another variant in exon 7, which leads to exon skipping, and is predicted to alter the ATP‐binding domain in MYO1F. Our study identified for the first time a role for MYO1F in NMTC.
USP4 expression independently predicts favorable survival in lung adenocarcinoma
Authors: Zhong Ming , Jiang Qi , Jin Ronghui
Published: April 2018

Ubiquitin specific protease 4 (USP4) is a member of the USPs family, which catalyzes the cleavage of ubiquitin from a series of protein substrates, thereby modulating a number of cellular signaling pathways. In this study, we aimed to explore the expression profile of USP4 in lung adenocarcinoma (LUAD) using large patient cohorts in the Cancer Genome Atlas and the International Cancer Genome Consortium and to investigate its prognostic value and the possible mechanisms of its dysregulation. Results showed that USP4 was significantly downregulated in LUAD tissues (N = 514) compared with the normal controls (N = 59). The high USP4 expression group had significantly better overall survival (OS) and recurrence‐free survival (RFS). Multivariate analysis showed that preserved USP4 expression was an independent prognostic factor of favorable OS (HR: 0.574, 95%CI: 0.427–0.771, P < 0.001) and RFS (HR: 0.625, 95%CI: 0.444–0.880, P = 0.007) in LUAD. In comparison, although USP4 was downregulated in lung squamous cell carcinoma, its expression had no prognostic value in term of OS and RFS. By examining USP4 DNA copy number alterations (CNAs) (N = 511) and DNA methylation (N = 453) in LUAD, we found that DNA shallow deletion was frequent (–1, N = 239, 46.8%) and was associated with significantly decreased USP4 expression compared with the copy‐neutral (0) cases. The methylation status of some CpG sites in USP4 DNA was negatively correlated with USP4 expression. Based on these findings, we infer that USP4 expression might be a favorable biomarker in terms of OS and RFS in LUAD patients. DNA shallow deletion and hypermethylation might be two important mechanisms of decreased USP4 in these patients. © 2018 IUBMB Life, 70(7):670–677, 2018
Human hepatocellular carcinoma: Protection by melatonin
Authors: Mortezaee Keywan
Published: April 2018

Despite great scientific breakthroughs toward understanding the identity of human hepatocellular carcinoma (HCC) mechanistically, there are still no clinically efficient therapeutic methods for this cancer. Melatonin (N‐acetyl‐5‐methoxytryptamine) is a multi‐tasking hormone that has long been known for its anti‐cancer activity against various human cancers including HCC, which is a focus of this review. PubMed database was searched for relevant articles with the keywords: hepatocellular carcinoma (HCC), melatonin, apoptosis, proliferation, invasion, angiogenesis, autophagy, oxidative stress, tumor immunity, and mitogen‐activated protein kinase (MAPK) focusing on just human cell lines and English language articles. Melatonin inhibits apoptosis resistance and activates both extrinsic and intrinsic pathways of apoptosis in HCC. Melatonin induces ensoplasmic reticulum (ER)‐ and autophagy‐mediated apoptosis in cancer cells. Melatonin works against cancer cell proliferation, motility, and invasiveness by modulating actions of a variety of transcription factors and related pathways. Melatonin also relieves an immunosuppressive state in HCC cancer cells through making a control over tumor‐derived exosomes. Both pro‐and anti‐oxidative functions of melatonin are necessary for combating HCC. Combination of melatonin with chemotherapy could also provide cumulative effects on cancer cells. Melatonin exerts most of these roles by acting on the members of MAPK family.
Baseline neutrophilia, derived neutrophil‐to‐lymphocyte ratio (dNLR), platelet‐to‐lymphocyte ratio (PLR), and outcome in non small cell lung cancer (NSCLC) treated with Nivolumab or Docetaxel
Authors: Russo Alessandro , Franchina Tindara , Ricciardi Giuseppina R.R. , Battaglia Alessandra , Scimone Antonino , Berenato Rosa , Giordano Antonio , Adamo Vincenzo
Published: April 2018

Nivolumab is a novel therapeutic option in NSCLC, associated with a significant survival gain compared with Docetaxel. However, predictive biomarkers are lacking. The presence of systemic inflammation has been correlated with poor outcome in many cancer types. We aimed to evaluate whether there is a correlation between some indicators of inflammation and response to Nivolumab or Docetaxel in pre‐treated NSCLCs. Data of 62 patients receiving Nivolumab or Docetaxel were analyzed. Baseline neutrophilia and thrombocytosis were not associated with response. High dNLR was associated with no response to Nivolumab, but not with Docetaxel, whereas high PLR correlated with low treatment response in both groups. Among refractory patients, a higher incidence of thrombocytosis, neutrophilia, high PLR, and high dNLR levels were observed compared with the overall population. This is one of the first reports in this field and suggests that indicators of inflammation might be included together with other predictive biomarkers in the baseline evaluation of patients candidate for immunotherapy.
Conventional and Microwave‐Activated the Synthesis of a Novel Series of Imidazoles, Pyrimidines, and Thiazoles Candidates
Authors: Selim Yasser , Abd El‐Azim Mohamed H. M.
Published: April 2018

A novel series of imidazoles, pyrimidines, and thiazoles were synthesized using microwave irradiation and conventional method from commercial available p‐aminobenzoic acid. Thus, one‐pot condensation of p‐aminobenzoic acid, urea, and chloroacetic acid have been provided two types of imidazole derivatives as separated mixture 2a and 2b. [3 + 2 + 1] Cyclocondensation of 2a, benzaldehyde, and urea/thiourea in acidic medium afforded imidazolo oxazine derivative 3 and Imidazolothiazine 4. Coupling of 2a with benzene diazonium salt gave the phenyldiazenyl imidazolidine 5. While the reaction of 2a, thiourea, and benzaldehyde in sodium ethoxide afforded imidazolothiazine 6. Oxidative cyclization of thiourea derivative 7 resulted a mixture of benzithiazole derivative 7a and oxathiazole derivative 7b. Cyclocondensation of 7a with phenylenediamine and 4‐methyl phenylenediamine furnished imidazole 8 and 9, respectively. Reaction of P‐aminobenzioc acid with potassium cyanate followed by Biginelli reaction with (acetyl acetone, ethyl acetoacetate, and diethyl malonate) and salicyladehyde in HCl tolerated pyrimidine derivatives 10a–c, respectively. In the same manner, the reactions and short reaction time make microwave technique one of the greenest methodology for synthesis of this class of heterocyclic system.
β2-Adrenoceptors inhibit neutrophil extracellular traps in human polymorphonuclear leukocytes
Authors: Marino Franca , Scanzano Angela , Pulze Laura , Pinoli Monica , Rasini Emanuela , Luini Alessandra , Bombelli Raffaella , Legnaro Massimiliano , de Eguileor Magda , Cosentino Marco
Published: April 2018

This study tests the hypothesis that in isolated human polymorphonuclear leukocytes (PMN) adrenergic ligands can affect neutrophil extracellular trap (NET) formation. We have previously shown that, in PMN, adrenaline (A), through the activation of adrenergic receptors (AR), reduces stimulus-dependent cell activation; we have, therefore, planned to investigate if AR are involved in NET production. PMN were obtained from venous blood of healthy subject. The ability of adrenergic ligands to affect reactive oxygen species (ROS) production, NET production, and cell migration was investigated in cells cultured under resting conditions or after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), LPS, or IL-8. Stimuli-induced NET production measured as ROS, microscopic evaluation, and elastase production was reverted by A and this effect was blocked by the selective β2–AR antagonist ICI-118,551. The stimulus-induced ROS generation and migration was prevented by A and by isoprenaline (ISO), and these effects were counteracted only by ICI-118,551 and not by the other two selective ligands for the β1 and β3–AR. Finally, the presence of the β–ARs on PMN was confirmed, by means of microscopy and flow cytometry. The data of the present study suggest that adrenergic compounds, through the interaction of mainly β2–AR, are able to affect neutrophil functions. These data are suggestive of a possible therapeutic role of β2–AR ligands (in addition to their classical use), promoting the possible therapeutic relevance of adrenergic system in the modulation of innate immunity proposing their possible use as anti-inflammatory drugs.

Adrenergic compounds modify NET production by human neutrophils and are able to affect other key functions of these cells.
Insight on the regulation of chemokine activities
Authors: Cecchinato Valentina , Uguccioni Mariagrazia
Published: April 2018

The activity of chemokines is regulated by several mechanisms that control the final cellular response. The present review discusses the complexity of the regulation of the chemokine system, and the novel findings describing how in persistent infections, the expression of chemokine receptors on the surface of T cells does not correlate with their homing potential. Thanks to the latest advances in our comprehension of the chemokine system, novel approaches targeting chemokines, chemokine receptors, or protein of their signaling pathway should be considered in order to achieve a personalized therapy.

Review focuses on the regulation of chemokine activities in health and disease.
Lipofection of plasmid DNA into human mast cell lines using lipid nanoparticles generated by microfluidic mixing
Authors: Duguay Brett A , Huang Kate Wei-Chen , Kulka Marianna
Published: April 2018

Mast cells are important immune cells that have significant roles in mediating allergy and asthma. Therefore, studying the molecular mechanisms regulating these and other processes in mast cells is important to elucidate. Methods such as lipofection, transduction, and electroporation are often employed to dissect these mechanisms by disrupting gene expression in mast cell lines. However, as with other leukocytes, human mast cells (HMCs) are often refractory to the delivery of plasmids by lipofection. In this study, we investigated the utility of lipid nanoparticles (LNPs) containing the ionizable cationic lipids 1,2-dioleoyloxy-3-dimethylaminopropane, 1,2-dioleyloxy-3-dimethylaminopropane, or 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane for the delivery of plasmid DNA into HMC lines. Herein, we demonstrate for the first time the use of LNPs to achieve significant and reproducible levels of plasmid DNA transfection in HMC-1.2 and laboratory of allergic diseases 2 (LAD2) cells. These levels reached 53.2% and 16.0% in HMC-1.2 and LAD2 cells, respectively; and outperformed Lipofectamine 3000 in both cases. Moreover, cell viability in the transfected cells remained above 65% for all LNP conditions tested. Together, these observations illustrate the efficacy of this technique for mast cell researchers and further support the use of LNPs for nucleic acid delivery into leukocytes.

Method based on DNA-lipid nanoparticles successfully and reproducibly transfects human mast cell lines while yielding levels of transgene expression and cell viability superior to traditional lipofection techniques.
A surface plasmon resonance assay for characterisation and epitope mapping of anti‐GLP‐1 antibodies
Authors: Thomsen Lasse , Gurevich Leonid
Published: April 2018

The incretin hormone glucagon‐like peptide‐1 (GLP‐1) has been subject to substantial pharmaceutical research regarding the treatment of type 2 diabetes mellitus. However, quantification of GLP‐1 levels remains complicated due to the low circulation concentration and concurrent existence of numerous metabolites, homologous peptides, and potentially introduced GLP‐1 receptor agonists. Surface plasmon resonance (SPR) facilitates real‐time monitoring allowing a more detailed characterisation of the interaction compared with conventional enzyme‐linked immunosorbent assays (ELISA). In this paper, we describe the development of the first SPR assays for characterisation of anti‐GLP‐1 antibodies for ELISA purposes. Binding responses were obtained on covalently immobilised anti‐GLP‐1 antibodies at 12°C, 25°C, and 40°C and fitted to a biomolecular (1:1) interaction model showing association rates of 1.01 × 103 to 4.54 × 103 M−1 s−1 and dissociation rates of 3.56 × 10−5 to 1.56 × 10−3 s−1 leading to affinities of 35.2 to 344 nM, depending on the temperature. Determination of thermodynamic properties revealed an enthalpy driven interaction (ΔH < ΔS < 0) with higher affinities at lower temperatures due to the formation and stabilisation of hydrogen bonds within the binding site primarily composed of polar amino acids (ΔCp < 0). Pair‐wise epitope mapping was performed on captured anti‐GLP‐1 antibodies followed by subsequent interaction with GLP‐1 (7‐36) and other anti‐GLP‐1 antibodies. A global evaluation of every binding response led to an epitope map elucidating the potential of various anti‐GLP‐1 antibody pairs for sandwich ELISA and hence pinpointing the optimal antibody combinations. The SPR assays proved capable of providing vital information for ELISA development endorsing it as a useful optimisation tool.
Fragmentation pathways and differentiation of positional isomers of sorafenib and structural analogues by ESI‐IT‐MSn and ESI‐Q‐TOF‐MS/MS coupled with DFT calculations
Authors: Yu Dandan , Liang Xianrui
Published: April 2018

Sorafenib is an orally active multikinase inhibitor for the treatment of renal cell carcinoma. A series of sorafenib structural analogues were investigated in this work for their gas‐phase fragmentation behaviors using electrospray ionization ion trap mass spectrometry and quadrupole time‐of‐flight mass spectrometry in the positive mode. The possible fragmentation pathways were proposed based on ESI‐MS/MS data and theoretical calculation. Different from the typical α‐cleavage of amide, consecutive reactions that involved elimination of H2O and CH3NC were observed for 2‐pyridinecarboxamide derivatives, which were followed by the formation of a stabilized 7‐membered ring carbocation by loss of CO. Two possible protonation sites occurred at carbonyl oxygen atoms for aryl‐urea derivatives and the α‐cleavage of urea was the main fragmentation pathways, which was followed by the formation of stable benzo [d] oxazole ring characteristic to aryl‐urea derivatives. The relative abundance of characteristic fragment ions and the energy‐resolved breakdown curves were used to distinguish the 4 sets of positional isomers of sorafenib and analogues. The methodology and results of the present work would contribute to the chemical structure identification of other structural analogues and the potential impurities presented in active pharmaceutical ingredients and drug formulations.
Integrating flipped drain and power gating techniques for efficient FinFET logic circuits
Authors: Dadoria Ajay Kumar , Khare Kavita , Gupta T.K. , Panwar Uday
Published: April 2018

Power dissipation is a main attention for designing complementary metal oxide semiconductor Very Large Scale Integration (VLSI) circuits in deep sub‐micron technology. Constant field device scaling leads to high transistor density, reduction in power supply, lower threshold voltage, and reduction in oxide thickness. This gives rise to short channel effects and increases the leakage currents causing power dissipation. In this paper, based on literature survey, new flipped drain gating (FDG) technique is proposed for mitigation of leakage currents; further FDG technique is integrated with power gating technique which makes power dissipation lower than FDG. Proposed techniques are integrated with FinFET technology and applied on Logic Gates and bench mark circuits on HSPICE simulator. Simulation is carried out at 27°C temperature by using 20 to 7‐nm Berkley Predictive Technology Module. Simulation results at 10‐MHz frequency shows maximum saving in leakage power using FDG technique at input vector 01 as 80.35% compared with conventional drain gating for EXOR logic. Similarly, FDG technique saves maximum dynamic power of 25.98% when compared with conventional drain gating for AND logic.
Spatial and temporal patterns of rainfall variability and its relationship with land surface phenology in central east Argentina
Authors: Celleri Carla , Zapperi Georgina , González Trilla Gabriela , Pratolongo Paula
Published: April 2018

Transition zones between dry and humid climates are highly sensitive areas where small changes in the spatial and temporal distribution of rainfall may have vast consequences on vegetation development. Rainfall regimes are expected to change worldwide and predictions include variations in total annual precipitation and timing of rain events. In this context, evaluating the relationship between vegetation activity and rainfall variability along transition zones is particularly relevant. In this study, 54 years (1961–2013) of gridded monthly rainfall data (Climatic Research Unit Time‐Series Version 3.22 [CRU TS3.22]) were used to analyse annual and inter‐annual rainfall variability. Land surface phenology (LSP) metrics (2000–2013) were derived from MODIS 16‐day composites Normalized Difference Vegetation Index (NDVI) data (MOD13Q1 product) and relationship between rainfall variability and LSP metrics was assessed. Annual rainfall showed a strong seasonality in the northeast of the study area that diminishes towards the southwest. Inter‐annual rainfall variability, which showed a significant 8‐year cycle periodicity after 1980, was stronger in the southwest of the region. For most of the study area, summer rainfall (November–January) showed significant negative correlation with August–October Southern Oscillation Index (SOI) average, although this connection was not reflected in annual precipitation totals. Regarding vegetation response to rainfall variability, two main areas were identified where differences in LSP metrics between wet and dry years were larger than the average. The first one was a zone within the humid to semi‐arid transition belt, where NDVI maximum, NDVI amplitude and NDVI integral showed higher values during wet years. The second one was the central north area, which showed higher NDVI amplitude values during dry years. In the study area, water availability is a sensitive issue for natural ecosystems, agriculture and cattle‐raising. These results provide a better understanding of the relationship between rainfall variability and vegetation changes, which is useful information for the development of future management policies.
Projected changes in temperature and precipitation extremes over the Silk Road Economic Belt regions by the Coupled Model Intercomparison Project Phase 5 multi‐model ensembles
Authors: Han Tingting , Chen Huopo , Hao Xin , Wang Huijun
Published: April 2018

The Silk Road Economic Belt and 21st‐century Maritime Silk Road is a development initiative proposed by the Chinese government. However, the Belt and Road regions involve a large population, and regional economic development is sensitive to climate change, particularly climate extreme events. Hence, it is of vital relevance to pay more attention to the climate extreme change over this region. In this study, changes in the temperature‐ and precipitation‐related extremes over the Belt and Road regions are evaluated during the middle and the end of this century using Coupled Model Intercomparison Project Phase 5 (CMIP5) simulations. Results present obvious changes in extreme temperature and precipitation indices under both RCP4.5 (representative concentration pathways) and RCP8.5 scenarios against the current climate state (1986–2005). Changes generally present relatively larger magnitudes under RCP8.5 than RCP4.5. Projected multi‐model ensemble results show a significant increase in warm events over Moscow and Nairobi. Additionally, cold events will decrease over central Europe, Moscow and central Asia, along with longer growing season length over these regions. The annual mean precipitation is reported to significantly increase over the region of Nairobi and the flooding events will be exacerbated across the Belt regions under a future warmer world, particularly over Moscow, Southeast Asia and Nairobi. Meanwhile, the region of West Asia will be likely to experience more drought and flooding events with the warming. However, we should also note that the inter‐model uncertainty of these results is reported to increase with time and a relatively large model spread can be seen in precipitation‐related indices when comparing with the temperature.
Vertical profile of cloud amount over Poland: Variability and uncertainty based on CloudSat–CALIPSO observations
Authors: Kotarba Andrzej Z.
Published: April 2018

Historically, climatologists have found it difficult to access reliable information on cloud vertical structure. This is because both surface‐based observers and imaging/sounding satellite sensors have limited capability to report superposed cloud. However, lidar–radar cloud profiles, collected between 2006 and 2011 by the experimental CloudSat and CALIPSO missions, offer an alternative source of data. This data set is explored to provide the very first analysis of cloud vertical structure over Poland. The study shows that the sky over Poland is dominated by low‐level cloud (33–35% at an altitude of 1–3 km), while cloud amounts at 5–10 km altitude are relatively constant (20%). Low‐level cloud is found to have the greatest seasonal (20% in July, 50% in January) and diurnal (30% daytime, 40% night‐time) variability. Uncertainty in the estimate of mean cloud amounts is shown to vary as a function of the number of profiles analysed, notably the time‐window used for data averaging. Uncertainty (measured as the width of the 95% confidence interval) ranged from a minimum of ±2% for the annual mean, to a maximum of ±10% for monthly means. The analysis demonstrated that uncertainty of below ±1% for the annual mean was only achievable if data were averaged over an area of 1,300 km2. A further finding was that surface‐based observers in Poland are unable to determine whether there are high‐level clouds up to 64% of the time, as these clouds are obscured by clouds at lower levels. Similarly, middle‐level clouds cannot be observed 55% of the time. These findings lead to the conclusion that CloudSat–CALIPSO observations remain the most reliable source of data on cloud vertical structure for Poland.
Process Monitoring of Laser Beam Melting
Authors: Hagedorn Yves , Pastors Felix
Published: April 2018

Powder bed laser melting (PBLM) is increasingly applied for series production in automotive, medicine and aerospace. Main drivers are extended design capabilities and steadily decreasing production costs. Nevertheless, process stability remains one central challenge for general industrial implementation. This challenge may be tackled by extensive process control, based on coaxial thermal emissivity sensing or high‐speed imaging. Towards this, the present work provides a first insight into the correlation of sensor data, applied process parameters and part properties.
A Great Year for the Industrial Laser Business in the USA
Authors: Belforte David A.
Published: April 2018

The global industrial laser business in 2017 experienced a record year in terms of revenues, topping the 4.3 billion dollars mark. From the end of the Great Recession (officially June 2009), according to Industrial Laser Solutions (ILS), market revenues grew at a 14.95 % CAGR for a 250 % increase over end of recession values (Fig. 1). Leading this charge were fiber laser revenues which rose at an exceptional 37.38 % CAGR to more than $2 B in 2017.
Perennial biomass production from marginal land in the Upper Mississippi River Basin
Authors: Feng Qingyu , Chaubey Indrajeet , Cibin Raj , Engel Bernard , Sudheer K.P. , Volenec Jeffrey , Omani Nina
Published: April 2018

Marginal land is considered promising for biomass production. However, understanding on biomass crop growth and total biofuel production from this land type is very limited. This study evaluated potential production of switchgrass (Panicum virgatum) and Miscanthus (Miscanthus × giganteus) on marginal lands in the Upper Mississippi River Basin. A soil and water assessment tool model with detailed representation of marginal lands and their suitability for growth of the 2 grasses was setup. Marginal land was defined as cropland and grassland with land capability class from 3 to 8. All marginal lands were included as new land covers in the land use map and were preserved when HRUs were defined. The soil and water assessment tool model was calibrated for flow at 13 sites within the Upper Mississippi River Basin region at monthly scale. The predicted biomass by growing switchgrass and Miscanthus on marginal lands in the study area can produce up to 37% of the 132 × 109 L biofuel goal set by the 2010 Energy Independence and Security Act in the USA. The simulated flow was lower when marginal lands were converted to grow perennial bioenergy crops. The results from this study improved our understanding on growth of perennial crops on marginal land and their contributions to biofuel development.
Clinical and imaging correlates of amyloid deposition in dementia with Lewy bodies
Authors: Donaghy Paul C. , Firbank Michael J , Thomas Alan J. , Lloyd Jim , Petrides George , Barnett Nicola , Olsen Kirsty , O'Brien John T.
Published: April 2018

Background: Amyloid deposition is common in dementia with Lewy bodies, but its pathophysiological significance is unclear.

Objective: The objective of this study was to investigate the relationship between amyloid deposition and clinical profile, gray matter volume, and brain perfusion in dementia with Lewy bodies.

Methods: Dementia with Lewy bodies (n = 37), Alzheimer's disease (n = 20), and controls (n = 20) underwent a thorough clinical assessment, 3T MRI, and early‐ and late‐phase 18F‐Florbetapir PET‐CT to assess cortical perfusion and amyloid deposition, respectively. Amyloid scans were visually categorized as positive or negative. Image analysis was carried out using statistical parametric mapping (SPM) 8.

Results: There were no significant differences between amyloid‐positive and amyloid‐negative dementia with Lewy bodies cases in age (P = .78), overall cognitive impairment (P = .83), level of functional impairment (P = .80), or any other clinical or cognitive scale. There were also no significant differences in hippocampal or gray matter volumes. However, amyloid‐positive dementia with Lewy bodies cases had lower medial temporal lobe perfusion (P = .03) than amyloid‐negative cases, although a combination of medial temporal lobe perfusion, hippocampal volume, and cognitive measures was unable to accurately predict amyloid status in dementia with Lewy bodies.

Conclusions: Amyloid deposition was not associated with differences in clinical or neuropsychological profiles in dementia with Lewy bodies, but was associated with imaging evidence of medial temporal lobe dysfunction. The presence of amyloid in dementia with Lewy bodies cannot be identified on the basis of clinical and other imaging features and will require direct assessment via PET imaging or CSF. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.