bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Deformation to Sea Ice Mass Balance: A Case Study From an N‐ICE2015 Storm
Authors: Itkin Polona , Spreen Gunnar , Hvidegaard Sine Munk , Skourup Henriette , Wilkinson Jeremy , Gerland Sebastian , Granskog Mats A.
Published: December 2017

The fastest and most efficient process of gaining sea ice volume is through the mechanical redistribution of mass as a consequence of deformation events. During the ice growth season divergent motion produces leads where new ice grows thermodynamically, while convergent motion fractures the ice and either piles the resultant ice blocks into ridges or rafts one floe under the other. Here we present an exceptionally detailed airborne data set from a 9 km2 area of first year and second year ice in the Transpolar Drift north of Svalbard that allowed us to estimate the redistribution of mass from an observed deformation event. To achieve this level of detail we analyzed changes in sea ice freeboard acquired from two airborne laser scanner surveys just before and right after a deformation event brought on by a passing low‐pressure system. A linear regression model based on divergence during this storm can explain 64% of freeboard variability. Over the survey region we estimated that about 1.3% of level sea ice volume was pressed together into deformed ice and the new ice formed in leads in a week after the deformation event would increase the sea ice volume by 0.5%. As the region is impacted by about 15 storms each winter, a simple linear extrapolation would result in about 7% volume increase and 20% deformed ice fraction at the end of the season.
Observations of the Proton Aurora on Mars With SPICAM on Board Mars Express
Authors: Ritter B. , Gérard J.‐C. , Hubert B. , Rodriguez L. , Montmessin F.
Published: December 2017

We report observations of the proton aurora at Mars, obtained with the Spectroscopy for the Investigation of the Characteristics of the Atmosphere of Mars (SPICAM) ultraviolet spectrograph on board Mars Express between 2004 and 2011. This is a third type of UV aurora that is discovered on Mars, in addition to the discrete and diffuse nightside aurora. It is observed only on the dayside as it is produced by the direct interaction of solar wind protons with the upper atmosphere. The auroral signature is an enhancement of the Lyman‐α emission in the order of a few kilorayleighs. The proton aurora features peak emissions around 120 to 150 km. From the full SPICAM database, limb observations have been investigated and six clear cases have been found. We identify either coronal mass ejections and/or corotating interaction regions as triggers for each of these events.
The Global Signature of Ocean Wave Spectra
Authors: Portilla‐Yandún Jesús
Published: December 2017

A global atlas of ocean wave spectra is developed and presented. The development is based on a new technique for deriving wave spectral statistics, which is applied to the extensive ERA‐Interim database from European Centre of Medium‐Range Weather Forecasts. Spectral statistics is based on the idea of long‐term wave systems, which are unique and distinct at every geographical point. The identification of those wave systems allows their separation from the overall spectrum using the partition technique. Their further characterization is made using standard integrated parameters, which turn out much more meaningful when applied to the individual components than to the total spectrum. The parameters developed include the density distribution of spectral partitions, which is the main descriptor; the identified wave systems; the individual distribution of the characteristic frequencies, directions, wave height, wave age, seasonal variability of wind and waves; return periods derived from extreme value analysis; and crossing‐sea probabilities. This information is made available in web format for public use at http://www.modemat.epn.edu.ec/#/nereo. It is found that wave spectral statistics offers the possibility to synthesize data while providing a direct and comprehensive view of the local and regional wave conditions.
Large Eddy Simulation of Heat Entrainment Under Arctic Sea Ice
Authors: Ramudu Eshwan , Gelderloos Renske , Yang Di , Meneveau Charles , Gnanadesikan Anand
Published: December 2017

Arctic sea ice has declined rapidly in recent decades. The faster than projected retreat suggests that free‐running large‐scale climate models may not be accurately representing some key processes. The small‐scale turbulent entrainment of heat from the mixed layer could be one such process. To better understand this mechanism, we model the Arctic Ocean's Canada Basin, which is characterized by a perennial anomalously warm Pacific Summer Water (PSW) layer residing at the base of the mixed layer and a summertime Near‐Surface Temperature Maximum (NSTM) within the mixed layer trapping heat from solar radiation. We use large eddy simulation (LES) to investigate heat entrainment for different ice‐drift velocities and different initial temperature profiles. The value of LES is that the resolved turbulent fluxes are greater than the subgrid‐scale fluxes for most of our parameter space. The results show that the presence of the NSTM enhances heat entrainment from the mixed layer. Additionally there is no PSW heat entrained under the parameter space considered. We propose a scaling law for the ocean‐to‐ice heat flux which depends on the initial temperature anomaly in the NSTM layer and the ice‐drift velocity. A case study of “The Great Arctic Cyclone of 2012” gives a turbulent heat flux from the mixed layer that is approximately 70% of the total ocean‐to‐ice heat flux estimated from the PIOMAS model often used for short‐term predictions. Present results highlight the need for large‐scale climate models to account for the NSTM layer.
Effects of Model Resolution and Ocean Mixing on Forced Ice‐Ocean Physical and Biogeochemical Simulations Using Global and Regional System Models
Authors: Jin Meibing , Deal Clara , Maslowski Wieslaw , Matrai Patricia , Roberts Andrew , Osinski Robert , Lee Younjoo J. , Frants Marina , Elliott Scott , Jeffery Nicole , Hunke Elizabeth , Wang Shanlin
Published: December 2017

The current coarse‐resolution global Community Earth System Model (CESM) can reproduce major and large‐scale patterns but is still missing some key biogeochemical features in the Arctic Ocean, e.g., low surface nutrients in the Canada Basin. We incorporated the CESM Version 1 ocean biogeochemical code into the Regional Arctic System Model (RASM) and coupled it with a sea‐ice algal module to investigate model limitations. Four ice‐ocean hindcast cases are compared with various observations: two in a global 1° (40∼60 km in the Arctic) grid: G1deg and G1deg‐OLD with/without new sea‐ice processes incorporated; two on RASM's 1/12° (∼9 km) grid R9km and R9km‐NB with/without a subgrid scale brine rejection parameterization which improves ocean vertical mixing under sea ice. Higher‐resolution and new sea‐ice processes contributed to lower model errors in sea‐ice extent, ice thickness, and ice algae. In the Bering Sea shelf, only higher resolution contributed to lower model errors in salinity, nitrate (NO3), and chlorophyll‐a (Chl‐a). In the Arctic Basin, model errors in mixed layer depth (MLD) were reduced 36% by brine rejection parameterization, 20% by new sea‐ice processes, and 6% by higher resolution. The NO3 concentration biases were caused by both MLD bias and coarse resolution, because of excessive horizontal mixing of high NO3 from the Chukchi Sea into the Canada Basin in coarse resolution models. R9km showed improvements over G1deg on NO3, but not on Chl‐a, likely due to light limitation under snow and ice cover in the Arctic Basin.
Mechanisms of Mixed‐Layer Salinity Seasonal Variability in the Indian Ocean
Authors: Köhler Julia , Serra Nuno , Bryan Frank O. , Johnson Benjamin K. , Stammer Detlef
Published: December 2017

Based on a joint analysis of an ensemble mean of satellite sea surface salinity retrievals and the output of a high‐resolution numerical ocean circulation simulation, physical processes are identified that control seasonal variations of mixed‐layer salinity (MLS) in the Indian Ocean, a basin where salinity changes dominate changes in density. In the northern and near‐equatorial Indian Ocean, annual salinity changes are mainly driven by respective changes of the horizontal advection. South of the equatorial region, between 45°E and 90°E, where evaporation minus precipitation has a strong seasonal cycle, surface freshwater fluxes control the seasonal MLS changes. The influence of entrainment on the salinity variance is enhanced in mid‐ocean upwelling regions but remains small. The model and observational results reveal that vertical diffusion plays a major role in precipitation and river runoff dominated regions balancing the surface freshwater flux. Vertical diffusion is important as well in regions where the advection of low salinity leads to strong gradients across the mixed‐layer base. There, vertical diffusion explains a large percentage of annual MLS variance. The simulation further reveals that (1) high‐frequency small‐scale eddy processes primarily determine the salinity tendency in coastal regions (in particular in the Bay of Bengal) and (2) shear horizontal advection, brought about by changes in the vertical structure of the mixed layer, acts against mean horizontal advection in the equatorial salinity frontal regions. Observing those latter features with the existing observational components remains a future challenge.
On the Climate Impacts of Upper Tropospheric and Lower Stratospheric Ozone
Authors: Xia Yan , Huang Yi , Hu Yongyun
Published: December 2017

The global warming simulations of the general circulation models (GCMs) are generally performed with different ozone prescriptions. We find that the differences in ozone distribution, especially in the upper tropospheric and lower stratospheric (UTLS) region, account for important model discrepancies shown in the ozone‐only historical experiment of the Coupled Model Intercomparison Project Phase 5 (CMIP5). These discrepancies include global high cloud fraction, stratospheric temperature, and stratospheric water vapor. Through a set of experiments conducted by an atmospheric GCM with contrasting UTLS ozone prescriptions, we verify that UTLS ozone not only directly radiatively heats the UTLS region and cools the upper parts of the stratosphere but also strongly influences the high clouds due to its impact on relative humidity and static stability in the UTLS region and the stratospheric water vapor due to its impact on the tropical tropopause temperature. These consequences strongly affect the global mean effective radiative forcing of ozone, as noted in previous studies. Our findings suggest that special attention should be paid to the UTLS ozone when evaluating the climate effects of ozone depletion in the 20th century and recovery in the 21st century. UTLS ozone difference may also be important for understanding the intermodel discrepancy in the climate projections of the CMIP6 GCMs in which either prescribed or interactive ozone is used.
Comment on “An Efficient and Stable Hydrodynamic Model With Novel Source Term Discretization Schemes for Overland Flow and Flood Simulations” by Xilin Xia et al.
Authors: Lu Xinhua , Mao Bing , Dong Bingjiang
Published: December 2017

Xia et al. (2017) proposed a novel, fully implicit method for the discretization of the bed friction terms for solving the shallow‐water equations. The friction terms contain h−7∕3 (h denotes water depth), which may be extremely large, introducing machine error when h approaches zero. To address this problem, Xia et al. (2017) introduces auxiliary variables (their equations (37) and (38)) so that h−4∕3 rather than h−7∕3 is calculated and solves a transformed equation (their equation (39)). The introduced auxiliary variables require extra storage. We implemented an analysis on the magnitude of the friction terms to find that these terms on the whole do not exceed the machine floating‐point number precision, and thus we proposed a simple‐to‐implement technique by splitting h−7∕3 into different parts of the friction terms to avoid introducing machine error. This technique does not need extra storage or to solve a transformed equation and thus is more efficient for simulations. We also showed that the surface reconstruction method proposed by Xia et al. (2017) may lead to predictions with spurious wiggles because the reconstructed Riemann states may misrepresent the water gravitational effect.
Effects of Heterogeneity, Connectivity, and Density Variations on Mixing and Chemical Reactions Under Temporally Fluctuating Flow Conditions and the Formation of Reaction Patterns
Authors: Pool Maria , Dentz Marco
Published: December 2017

Solute mixing, spreading, and fast chemical reactions in aquifers are strongly influenced by spatial variability of the hydraulic properties, temporal flow fluctuations, and fluid density differences. We study the coupling of heterogeneity, transient forcing, and density‐driven flow on mixing and chemical reactions between two fluids of different density under a stable stratification. We consider the reaction of the fast dissolution of calcite. We find that temporal fluctuations and heterogeneity cause strong local enhancement of the mixing and reaction rates and this impact increases with the degree of connectivity of hydraulic conductivity. The global mixing and reactivity, however, are on the order of or smaller than their homogeneous counterparts due to heterogeneity‐induced fluid segregation. The local maxima of the mixing and reaction rates are found to be located around strongly stretched regions corresponding to high velocity zones where dispersive mass transfer mechanisms are increased by dispersion. We also find that density variations compress the interface, which in turn emphasizes local maxima in mixing and reaction rates. Numerical results provide evidence that the stretching of the interface induced by spatial heterogeneity and transient effects coupled with density variations lead to the formation of complex patterns of reactive hotspots, zones of enhanced reaction efficiency, and that its distribution is directly linked to the deformation properties and topology of the flow field. These results provide new insights into the role of spatial and temporal variability on the mixing and reaction efficiency as well as the formation of reactive geochemical patterns in actual environmental systems.
High‐Performance, Self‐Driven Photodetector Based on Graphene Sandwiched GaSe/WS2 Heterojunction
Authors: Lv Quanshan , Yan Faguang , Wei Xia , Wang Kaiyou
Published: December 2017

Restacking the exfoliated 2D layered materials into complex heterostructures with new functionality has opened a new platform for materials engineering and device application. In this work, graphene sandwiched p‐GaSe/n‐WS2 vertical heterostructures are fabricated for photodetection. The devices show excellent performance on photodetection from ultraviolet to visible wavelength range, including high photoresponsivity (≈149 A W−1 at 410 nm), short response time of 37 µs, and self‐powered photodetection. The scanning photocurrent microscopy is also employed to investigate the photocurrent generation in the heterojunction and a significant enhancement of the photoresponse is found in the overlapping region. The results suggest that the graphene sandwiched vertical heterojunctions are promising in future novel optoelectronic devices applications.
Synthesis of polycarboxylate superplasticizers using an acrylic acid‐rich wastewater from acrolein production
Authors: Pei Jikai , Wang Ziwei , Ren Jianguo , Liu Diansheng
Published: December 2017

In this paper, an acrylic acid‐rich wastewater from the production of propylene to acrolein was used to synthesize the polycarboxylate superplasticizers. First, the acrylic acid‐rich wastewater was oxidized. Then, two kinds of unsaturated polyether macromonomers {methallyl polyethylene glycol (HPEG) and isoprenol polyethylene glycol (IPEG)} and the oxidized wastewater were copolymerized with it, respectively, by free radical polymerization in aqueous solution. The monomer conversion, molecular weight, molecular weight distribution of the copolymers of gel permeation chromatography (GPC) were characterized. The performance of the two copolymers was characterized by measuring paste flow, adsorption using GPC method, and the applied behavior of premixed concrete. The results showed that the synthesized copolymers could meet the requirement of application in contrast to the commodity product.
Height–income association in developing countries: Evidence from 14 countries
Authors: Patel Pankaj C. , Devaraj Srikant
Published: December 2017

Objectives

The purpose of this study was to assess whether the height–income association is positive in developing countries, and whether income differences between shorter and taller individuals in developing countries are explained by differences in endowment (ie, taller individuals have a higher income than shorter individuals because of characteristics such as better social skills) or due to discrimination (ie, shorter individuals have a lower income despite having comparable characteristics).

Methods

Instrumental variable regression, Oaxaca–Blinder decomposition, quantile regression, and quantile decomposition analyses were applied to a sample of 45 108 respondents from 14 developing countries represented in the Research on Early Life and Aging Trends and Effects (RELATE) study.

Results

For a one‐centimeter increase in country‐ and sex‐adjusted median height, real income adjusted for purchasing power parity increased by 1.37%. The income differential between shorter and taller individuals was explained by discrimination and not by differences in endowments; however, the effect of discrimination decreased at higher values of country‐ and sex‐adjusted height.

Conclusions

Taller individuals in developing countries may realize higher income despite having characteristics similar to those of shorter individuals.
Vasodilator dysfunction and oligodendrocyte dysmaturation in aging white matter
Authors: Bagi Zsolt , Brandner Dieter D. , Le Phuong , McNeal David W. , Gong Xi , Dou Huijuan , Fulton David J. , Beller Allison , Ngyuen Thuan , Larson Eric B. , Montine Thomas J. , Keene C. Dirk , Back Stephen A.
Published: December 2017

Objective

Microvascular brain injury (mVBI) is a common pathological correlate of vascular contributions to cognitive impairment and dementia (VCID) that leads to white matter (WM) injury (WMI). VCID appears to arise from chronic recurrent white matter ischemia that triggers oxidative stress and an increase in total oligodendrocyte lineage cells. We hypothesized that mVBI involves vasodilator dysfunction of white matter penetrating arterioles and aberrant oligodendrocyte progenitor cell (OPC) responses to WMI.

Methods

We analyzed cases of mVBI with low Alzheimer's disease neuropathological change in prefrontal cortex WM from rapid autopsies in a population‐based cohort where VCID frequently occurs. Arteriolar vasodilator function was quantified by videomicroscopy. OPC maturation was quantified using lineage specific markers.

Results

Acetylcholine‐mediated arteriolar dilation in mVBI was significantly reduced in WM penetrators relative to pial arterioles. Astrogliosis‐defined WMI was positively associated with increased OPCs and was negatively associated with decreased mature oligodendrocytes.

Interpretation

Selectively impaired vasodilator function of WM penetrating arterioles in mVBI occurs in association with aberrant differentiation of OPCs in WMI, which supports that myelination disturbances in VCID are related to disrupted maturation of myelinating oligodendrocytes. Ann Neurol 2018;83:142–152
Carbon Monoxide Oxidation by Polyoxometalate‐Supported Gold Nanoparticulate Catalysts: Activity, Stability, and Temperature‐ Dependent Activation Properties
Authors: Yoshida Takuya , Murayama Toru , Sakaguchi Norihito , Okumura Mitsutaka , Ishida Tamao , Haruta Masatake
Published: December 2017

Nanoparticulate gold supported on a Keggin‐type polyoxometalate (POM), Cs4[α‐SiW12O40]⋅n H2O, was prepared by the sol immobilization method. The size of the gold nanoparticles (NPs) was approximately 2 nm, which was almost the same as the size of the gold colloid precursor. Deposition of gold NPs smaller than 2 nm onto POM (Au/POM) was essential for a high catalytic activity for CO oxidation. The temperature for 50 % CO conversion was −67 °C. The catalyst showed extremely high stability for at least one month at 0 °C with full conversion. The catalytic activity and the reaction mechanism drastically changed at temperatures higher than 40 °C, showing a unique behavior called a U‐shaped curve. It was revealed by IR measurement that Auδ+ was a CO adsorption site and that adsorbed water promoted CO oxidation for the Au/POM catalyst. This is the first report on CO oxidation utilizing Au/POMs catalysts, and there is a potential for expansion to various gas‐phase reactions.
Design of the First‐in‐Class, Highly Potent Irreversible Inhibitor Targeting the Menin‐MLL Protein–Protein Interaction
Authors: Xu Shilin , Aguilar Angelo , Xu Tianfeng , Zheng Ke , Huang Liyue , Stuckey Jeanne , Chinnaswamy Krishnapriya , Bernard Denzil , Fernández‐Salas Ester , Liu Liu , Wang Mi , McEachern Donna , Przybranowski Sally , Foster Caroline , Wang Shaomeng
Published: December 2017

The structure‐based design of M‐525 as the first‐in‐class, highly potent, irreversible small‐molecule inhibitor of the menin‐MLL interaction is presented. M‐525 targets cellular menin protein at sub‐nanomolar concentrations and achieves low nanomolar potencies in cell growth inhibition and in the suppression of MLL‐regulated gene expression in MLL leukemia cells. M‐525 demonstrates high cellular specificity over non‐MLL leukemia cells and is more than 30 times more potent than its corresponding reversible inhibitors. Mass spectrometric analysis and co‐crystal structure of M‐525 in complex with menin firmly establish its mode of action. A single administration of M‐525 effectively suppresses MLL‐regulated gene expression in tumor tissue. An efficient procedure was developed to synthesize M‐525. This study demonstrates that irreversible inhibition of menin may be a promising therapeutic strategy for MLL leukemia.
Investigations on matrix network characteristics in NBR/silica nanocomposites: Resolving matrix bulk density and network molecular weight and their alterations due to filler‐curing agent interactions
Authors: Khabiri Mohammad , Jafari Seyed Hassan , Pourhossaini Mohammad Reza , Khonakdar Hossein Ali
Published: December 2017

Presence of filler in an elastomeric composite can affect curing characteristics due to possible interaction with curing agents. Alteration of the curing characteristics can change intrinsic properties of elastomer including its bulk density and swelling behavior. In this study, a series of acrylonitrile butadiene rubber (NBR) with various curing levels was prepared. From the experimental data the bulk density and network molecular weight (Mc,sw) were specified and a relationship was established between these parameters. In order to determine the swelling characteristics of NBR in presence of filler, another series of NBR/silica nanocomposites was prepared with various nanosilica loadings under a constant content of curing agents and curing conditions. With the use of the swelling data and applying the obtained relationship, the Mc,sw and bulk density of the filled NBR matrix were resolved. The Mc,sw values obtained by considering the influence of nanosilica on curing characteristics of NBR were compared with those obtained simply based on bulk density of raw rubber. This comparison confirmed that there are considerable differences between these values. With increasing nanosilica contents, and hence, increasing the negative impact of the filler on reducing curing degree of NBR, the bulk density of filled NBR matrix was decreased. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46170.
UV and corrosion protective behavior of polymer hybrid coating on mild steel
Authors: Pugazhenthi I. , Mohammed Safiullah S. , Anver Basha K.
Published: December 2017

Poly[(pyridine‐4‐yl‐methyl)methacrylate‐co‐butyl methacrylate] [poly(PyMMA‐co‐BMA)] and its ZnO nanocomposites [poly(PyMMA‐co‐BMA)/ZnO] were coated on the mild steel substrate (MS) to improve the corrosion resistance by blocking the destructive ultraviolet radiation (UV‐radiation) and corrosive ions as well. The optical and anticorrosive properties of poly(PyMMA‐co‐BMA) and poly(PyMMA‐co‐BMA)/ZnO (1.0, 1.5, and 2.5 wt %) coatings were evaluated. The surface characterization techniques like UV visible spectroscopy and scanning electron microscope were taken to confirm the formation of poly(PyMMA‐co‐BMA) and poly(PyMMA‐co‐BMA)/ZnO (2.5 wt %) coating on MS. The optical studies revealed that the poly(PyMMA‐co‐BMA)/ZnO (2.5 wt %) coating displays excellent UV blocking properties than other nanocomposite coatings (1.0 and 1.5 wt %). The potentiodynamic polarization and electrochemical impedance spectroscopy studies show that the poly(PyMMA‐co‐BMA) and poly(PyMMA‐co‐BMA)/ZnO (1.0, 1.5, and 2.5 wt %) coated MS in 3.5% (w/v) NaCl provides better protection against corrosion. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46175.
Polysulfobetaine bearing tertiary amide between counterions and its applications
Authors: Arjunan Vasantha Vivek , Oh Biying Algin , Parthiban Anbanandam
Published: December 2017

Modified sulfobetaine bearing tertiary amide spacer between the counterions is synthesized and polymerized by reversible addition–fragmentation chain transfer polymerization technique. The tertiary amide spacer influences various characteristics of the zwitterionic polymer. The modified polyzwitterion, PZI, forms coacervates in deionized water. The coacervates are thoroughly characterized by scanning electron microscopy, transmission electron microscopy, and transmittance studies. The ability to form coacervate complexes with functional ingredients has been demonstrated by encapsulating renewable resource actives like ferulic acid. The coacervate complexes have been studied by optical microscopy, transmission electron microscopy, and automated sunscreen sun protection factor analyzer. Synergism is noticed in the coacervate complex. Because of its ability to form self‐coacervates, this novel addition to the zwitterionic family is potentially useful for encapsulating many functional ingredients through coacervate complex formation. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46178.
Coming to Terms with the Authoritarian Alternative: The Implications and Motivations of China's Environmental Policies
Authors: Beeson Mark
Published: December 2017

China has assumed a crucial importance in debates about climate change mitigation. On the one hand, China is one of the largest emitters of greenhouse gasses and pollution. On the other, it has invested more in renewable energy than any other country and is making real efforts to address the consequences of rapid industrialisation. There are three key questions for students of comparative political economy that emerge from the Chinese experience: first, what is the relationship between economic development and authoritarian rule? Second, what role has China's distinct social and political system played in creating and addressing environmental problems? Third, what domestic and international implications does the ‘China model’ have? In short, will China's authoritarian leaders be able to manage the expectations of its own people and those of the so‐called international community? This article considers the often paradoxical and contradictory nature of the authoritarian Chinese government's current environmental policies and suggests that while they may have some success at the domestic level, they may still be an obstacle to international cooperation.
Oxaprozin prodrug as safer nonsteroidal anti‐inflammatory drug: Synthesis and pharmacological evaluation
Authors: Peesa Jaya P. , Atmakuri Lakshmana R. , Yalavarthi Prasanna R. , Mandava Venkata Basaveswara R. , Rasheed Arun , Pachava Vengalrao
Published: December 2017

Oxaprozin is a popular non‐steroidal anti‐inflammatory drug (NSAID) and its chronic oral use is clinically restricted due to its gastrointestinal (GI) complications. In order to circumvent the GI complications, oxaprozin was amended as a prodrug in a one‐pot reaction using N,N‐carbonyldiimidazole as an activating agent. Dextran of average molecular weight (60,000–90,000 Da) was exploited as a carrier in the process of oxaprozin prodrug production by esterification. The structural profiles of the synthesized oxaprozin prodrug were characterized by FT‐IR and NMR spectroscopy. The oxaprozin prodrug possessed optimal molecular weight, lipophilicity, partition coefficient, protein binding, and degree of substitution of 52.4%. The release of oxaprozin upon hydrolysis of the prodrug in both simulated gastric fluid and simulated intestinal fluid followed first‐order kinetics with 55.2 min of half‐life. Varied ADME properties of the prodrug resulted upon Schrodinger's QikProp tool application. Oxaprozin prodrug displayed significant analgesic, antipyretic, and anti‐inflammatory activities, with a remarkable decrease in the ulcer index and being devoid of antigenicity in experimental animals. Thus, it is evident that oxaprozin prodrug is a safer oral NSAID without causing any ulcerations.
Effects of HLA–B27 on Gut Microbiota in Experimental Spondyloarthritis Implicate an Ecological Model of Dysbiosis
Authors: Gill Tejpal , Asquith Mark , Brooks Stephen R. , Rosenbaum James T. , Colbert Robert A.
Published: December 2017

Objective

To investigate whether HLA–B27–mediated experimental spondyloarthritis (SpA) is associated with a common gut microbial signature, in order to identify potential drivers of pathogenesis.

Methods

The effects of HLA–B27 on 3 genetic backgrounds, dark agouti (DA), Lewis, and Fischer, were compared, using wild‐type littermates and HLA–B7–transgenic Lewis rats as controls. Cecum and colon tissue specimens or contents were collected from the rats at 2, 3–4, and 6–8 months of age, and histologic analysis was performed to assess inflammation, RNA sequencing was used to determine gene expression differences, and 16S ribosomal RNA gene sequencing was used to determine microbiota differences.

Results

Both HLA–B27–transgenic Lewis rats and HLA–B27–transgenic Fischer rats developed gut inflammation, while DA rats were resistant to the effects of HLA–B27, and HLA–B7–transgenic rats were not affected. Immune dysregulation was similar in affected Lewis and Fischer rats and was dominated by activation of interleukin‐23 (IL‐23)/IL‐17, interferon, tumor necrosis factor, and IL‐1 cytokines and pathways in the colon and cecum, while DA rats exhibited low‐level cytokine dysregulation without inflammation. Gut microbial changes in HLA–B27–transgenic rats were strikingly divergent on the 3 different host genetic backgrounds, including different patterns of dysbiosis in HLA–B27–transgenic Lewis and HLA–B27–transgenic Fischer rat strains, with some overlap. Interestingly, DA rats lacked segmented filamentous bacteria that promote CD4+ Th17 cell development, which may explain their resistance to disease.

Conclusion

The effects of HLA–B27 on gut microbiota and dysbiosis in SpA are highly dependent on the host genetic background and/or environment, despite convergence of dysregulated immune pathways. These results implicate an ecological model of dysbiosis, with the effects of multiple microbes contributing to the aberrant immune response, rather than a single or small number of microbes driving pathogenesis.
An operational fog prediction system for Delhi using the 330 m Unified Model
Authors: Jayakumar A. , Rajagopal E. N. , Boutle Ian A. , George John P. , Mohandas Saji , Webster Stuart , Aditi S.
Published: December 2017

We introduce the National Centre for Medium Range Weather Forecasting's (NCMRWF) high‐resolution (330 m) Unified Model implementation targeted at fog and visibility prediction over Delhi, the “Delhi Model” (DM). The requirement for running the DM in real time is that Delhi is highly vulnerable to fog‐related issues and that low visibility conditions affect both airborne and ground transport during winter months. Enhanced orographic features at 330 m resolution, in conjunction with other surface boundary conditions used by the DM, have led to improvements in the simulation of spatio‐temporal variability of visibility. During the winter season, the increased levels of pollution can have a significant impact on fog, or smog formation. Sensitivity experiments carried out using specified aerosol mass concentrations show that the visibility predicted by the DM is highly sensitive to the presence of aerosol. The impact of the urban heat island on visibility prediction is also investigated using recent high‐resolution land use data from the Indian Space Research Organisation (ISRO) in the model.
Noise in the Machine: Alternative Pathway Sampling is the Rule During DNA Replication
Authors: Scherr Matthias J. , Safaric Barbara , Duderstadt Karl E.
Published: December 2017

The astonishing efficiency and accuracy of DNA replication has long suggested that refined rules enforce a single highly reproducible sequence of molecular events during the process. This view was solidified by early demonstrations that DNA unwinding and synthesis are coupled within a stable molecular factory, known as the replisome, which consists of conserved components that each play unique and complementary roles. However, recent single‐molecule observations of replisome dynamics have begun to challenge this view, revealing that replication may not be defined by a uniform sequence of events. Instead, multiple exchange pathways, pauses, and DNA loop types appear to dominate replisome function. These observations suggest we must rethink our fundamental assumptions and acknowledge that each replication cycle may involve sampling of alternative, sometimes parallel, pathways. Here, we review our current mechanistic understanding of DNA replication while highlighting findings that exemplify multi‐pathway aspects of replisome function and considering the broader implications.
Rapid, controllable, one‐pot and room‐temperature aqueous synthesis of ZnO:Cu nanoparticles by pulsed UV laser and its application for photocatalytic degradation of methyl orange
Authors: Arabi Mozhgan , Baizaee Seyyed Mahdy , Bahador Alireza , Otaqsara Seyed Mohammad Taheri
Published: December 2017

Zinc oxide (ZnO) and ZnO:Cu nanoparticles (NPs) were synthesized using a rapid, controllable, one‐pot and room‐temperature pulsed UV‐laser assisted method. UV‐laser irradiation was used as an effective energy source in order to gain better control over the NPs size and morphology in aqueous media. Parameters effective in laser assisted synthesis of NPs such as irradiation time and laser shot repetition rate were optimized. Photoluminescence (PL) spectra of ZnO NPs showed a broad emission with two trap state peaks located at 442 and 485 nm related to electronic transition from zinc interstitial level (IZn) to zinc vacancy level (VZn) and electronic transition from conduction band to the oxygen vacancy level (VO), respectively. For ZnO:Cu NPs, trap state emissions disappeared completely and a copper (Cu)‐related emission appeared. PL intensity of Cu‐related emission increased with the increase in concentration of Cu2+, so that for molar ratio of Cu:Zn 2%, optimal value of PL intensity was obtained. The photocatalytic activity of Cu‐doped ZnO revealed 50 and 100% increasement than that of undoped NPs under UV and visible irradiation, respectively. The enhanced photocatalytic activity could be attributed to smaller crystal size, as well as creation of impurity acceptor levels (T2) inside the ZnO energy band gap.
Antimetastatic Activity of Gallic Acid‐conjugated Chitosan against Pulmonary Metastasis of Colon Carcinoma Cells
Authors: Lee Hye Lim , Choi Cheol Woong , Kim Jungsoo , Cha Byungyoul , Nah Jae Woon , Hong Jeong Sup , Hwang Sung Chul , Jeong Young‐IL , Kang Dae Hwan
Published: December 2017

We synthesized gallic acid (GA)‐conjugated chitosan (abbreviated as chitogallate) to study its antitumor activity against CT26 mouse colorectal carcinoma cells. GA was conjugated with chitosan by aid of water‐soluble carbodiimide. Chitogallate nanoparticles were prepared by dialysis method, and these nanoparticles have spherical shapes with sizes ranged about 70–250 nm. Chitogallate nanoparticles have superior antioxidants activities as well as GA itself. At cytotoxicity study, GA showed dose‐dependent cytotoxicities against CCD986sk cells and CT26 cells while chitogallate nanoparticles were not significantly affected to the viability of cells. In Matrigel invasion assay, chitogallate nanoparticles have superior anti‐invasive capacity against cancer cells as well as GA itself, i.e., invasiveness of CT26 cells was decreased according to GA contents in chitogallate nanoparticles. Furthermore, gelatin zymography also showed that chitogallate nanoparticles having higher substitution degree of GA decreased matrix metalloproteinase‐2 activity. Chitogallate nanoparticles efficiently inhibited pulmonary metastasis of CT26 cells in animal pulmonary metastasis model. We prepared chitogallate nanoparticles for application as an anti‐invasive agent. Chitogallate nanoparticles were less toxic than GA itself and have superior anti‐invasive/antimetastatic activity. We suggest that chitogallate nanoparticles are promising candidate for inhibition of tumor invasion/metastasis.
Grade distribution digests: A novel tool to enhance teaching and student learning in laboratory practicals
Authors: Arthur Peter G. , Zareie Reza , Kirkwood Paul , Ludwig Martha , Attwood Paul V.
Published: December 2017

Assessment is a central component of course curriculums and is used to certify student learning, but it can also be used as a tool to improve teaching and learning. Many laboratory courses are structured such that there is only a grade for a particular laboratory, which limits the insights that can be gained in student learning. We developed a laboratory program that incorporates assessments designed to probe student understanding of different components of the individual modules making up the program. The challenge was to analyze and present grades from these assessment tasks in a format that was readily interpretable by academics. We show that a simplified synthesis of grade distributions (grade distribution digests) provides sufficient information to make decisions about changes in course components. The main feature of the digests is its data visualization approach, where student grades for individual laboratory practicals, individual assessment tasks or individual assessment items are graphically presented as an overall average grade, an average top quartile grade and an average bottom quartile grade, and relative averages across all assessments. This ability to visualize student grades in variety of contexts enables academics with many other demands on their time (e.g. research and administration) to more efficiently identify ways to improve teaching delivery and learning outcomes. Examples are presented of the use of such data to identify and improve deficiencies in both student skills and teaching practice, resulting in improved learning outcomes. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(2):130–140, 2018.
Update on research and application of problem‐based learning in medical science education
Authors: Fan Chuifeng , Jiang Biying , Shi Xiuying , Wang Enhua , Li Qingchang
Published: December 2017

Problem‐based learning (PBL) is a unique form of pedagogy dedicated to developing students' self‐learning and clinical practice skills. After several decades of development, although applications vary, PBL has been recognized all over the world and implemented by many medical schools. This review summarizes and updates the application and study of PBL in medical education through the literature published between 1993 and early 2017. It focuses on understanding real medical PBL courses and ways to improve PBL to achieve better learning outcomes. PBL aims to develop lifelong skills to solve practical problems rather than limiting learning to theoretical knowledge. To achieve this goal, strict and reasonable procedures need to be designed and implemented. Rigorous monitoring and timely feedback and evaluation are indispensable to constant improvements and perfecting of the process. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(2):186–194, 2018.
Rational Design, Binding Studies, and Crystal‐Structure Evaluation of the First Ligand Targeting the Dimerization Interface of the 14‐3‐3ζ Adapter Protein
Authors: Ehlers Martin , Grad Jean‐Noël , Mittal Sumit , Bier David , Mertel Marcel , Ohl Ludwig , Bartel Maria , Briels Jeroen , Heimann Marius , Ottmann Christian , Sanchez‐Garcia Elsa , Hoffmann Daniel , Schmuck Carsten
Published: December 2017

14‐3‐3 Proteins play a central role in signalling pathways in cells: they interact as gatekeeper proteins with a huge number of binding partners. Their function as hub for intracellular communication can explain why these adapter proteins are associated with a wide range of diseases. How they control the various cellular mechanisms is still unclear, but it is assumed that the dimeric nature of the 14‐3‐3 proteins plays a key role in their activity. Here, we present, to the best of our knowledge, the first example of a small molecule binding to the 14‐3‐3ζ dimerisation interface. This compound was designed by rational in silico optimisation of a peptidic ligand identified from biochemical screening of a peptidic library, and the binding was characterised by UV/Vis spectroscopy, microscale thermophoresis, multiscale simulations, and X‐ray crystallography.
Knockdown of CPEB4 expression suppresses cell migration and invasion via Akt pathway in non‐small cell lung cancer
Authors: Hu Jing , Zhang LiBin , Chen Qiang , Lin Jie , Wang ShaoBo , Liu Ri , Zhang WenJing , Miao Kun , Shou Tao
Published: December 2017

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) could be an important regulator in variety of cancers. However, the biological function and the underlying molecular mechanism of CPEB4 in non‐small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the metastasis role of CPEB4 in NSCLC cells, we knocked down CPEB4 using siRNA. Transwell migration assay and cell invasion assay on Matrigel were presented, and cell migration was also determined by scratch‐healing assay. ROS generation were determined by fluorescence probe DCFH2‐DA. The protein expression was assessed by ELISA and Western blot analysis. LY294002 were used to inhibit PI3 K/Akt signaling. The data showed that knockdown of CPEB4 inhibited the migration and invasion of NSCLC. Moreover, silencing of CPEB4 reduced Snail and MMP‐3 expression in vitro. We also indicated that CPEB4 knockdown increased the ROS expression. Furthermore, we found that silencing of CPEB4 decreased pAkt expression. Taken all together, our data demonstrated that silencing of CPEB4 induces ROS generation, thus suppressing the Akt expression, which finally prevents NSCLC cells invasion and migration. Therefore, CPEB4 may regard as a target to inhibit NSCLC invasion and metastasis through Akt pathway.
Molecular modeling and chemometric analysis of osteoporosis calmodulin‐TRPV1 binding affinity by statistically characterizing complex interactions
Authors: Liu Xudong , Zhu Limin , Wang Lei , Yu Lingzhi , Gao Cong
Published: December 2017

The intermolecular interaction among the calcium sensor, calmodulin (CaM), and the C‐terminal domain of its cognate partner, transient receptor potential vanilloid 1 (TRPV1), plays a potential role in bone absorption and loss, which has been recognized as a new druggable target for osteoporosis therapy. Here, a synthetic strategy that integrates molecular modeling and chemometric analysis is used to statistically model and quantitatively predict the binding behavior of TRPV1 to CaM. The atomic‐level complex structures of CaM protein with the congeneric sequences of TRPV1 C‐terminus are modeled by virtual mutagenesis and structural refinement. Inter‐residue nonbonded interactions in the computationally modeled complex structures are analyzed, characterized, and correlated with experimentally measured affinity of CaM binding to a series of TRPV1 C‐terminal derivatives via both linear and nonlinear regression approaches. The built statistical predictors are then used to systematically investigate the independent residue‐pair interactions across CaM‐TRPV1 complex interface. Consequently, few TRPV1 C‐terminal residues are identified as potential hot spots that are primarily responsible for the CaM‐TRPV1 binding. Visual examination of CaM‐TRPV1 complex architecture reveals that these hot spot residues are evenly distributed through the core helical region of TRPV1 C‐terminus and involved in short‐range nonbonded interactions such as hydrogen bonds and salt bridges, which confer specificity to the complex recognition and association.
Chromatographic and in silico assessment of logP measures for new spirohydantoin derivatives with anticancer activity
Authors: Djaković Sekulić Tatjana , Smoliński Adam , Mandić Anamarija , Lazić Anita
Published: December 2017

Lipophilicity has, for a long time, been recognized as a meaningful parameter in structure‐activity relationships. It is also the single most informative physicochemical property that reveals a wealth of information on intermolecular forces, intramolecular interactions, and molecular structure in the broadest sense. In this paper, a total of 14 chromatographic measures of lipophilicity (thin‐layer chromatography and high‐performance liquid chromatography) and 11 computationally estimated logP‐s for 21 newly synthesized 3‐(4‐substituted benzyl)‐cycloalkylspiro‐5‐hidantoin derivatives have been investigated. Similarities among the investigated compounds as well as lipophilicity measures were examined by the multivariate exploratory analysis, principal component analysis, hierarchical cluster analysis, and sum of ranking differences. These chemometric approaches reveal the arrangement of investigated compounds into clusters according to lipophilicity. Chemometric consideration of lipophilicity renders principal component scores as entirely unsuitable lipophilicity measures. Furthermore, the logP values estimated from calibration graph by using a set of standard reference compounds were equivalent to the corresponding chromatographic descriptors of hydantoins extrapolated from linear relationship between retention parameters and mobile phase composition. Comparison of the 2 chromatographic techniques places high‐performance liquid chromatography lipophilicity indices slightly ahead of thin‐layer chromatography.