bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosimetric comparison of TMR10 and convolution dose calculation algorithms in GammaPlan treatment planning system
Authors: Kendall Ethan , Algan Ozer , Chen Yong , Ahmad Salahuddin
Published: June 2019

Aims:

In this article, our goal is to compare the TMR10 and convolution dose calculation algorithm in GammaPlan used in stereotactic radiosurgery (SRS) treatments with Gamma Knife and to assess if the algorithms produce clinically significant differences.

Materials and methods:

Treatment plans were analysed from ten patients who have undergone Gamma Knife SRS treatments. Patient plans were retrospectively recalculated using Lesksell GammaPlan 10 treatment software utilising the TMR10 and convolution dose calculation algorithms in order to create a paired dataset for comparison. Evaluation was based on the dose volume histogram (parameters of minimum, mean, maximum and integral doses.

Results:

The ratios of average integral doses calculated by the convolution dose calculation algorithm to the average integral doses calculated by the TMR10 algorithm are 0·997 for the target (p=0·028), 1·048 (p=0·48) for the skull and 1·005 (p=0·68) for the brainstem.

Conclusions:

Although doses calculated with the convolution algorithm resulted in slightly higher mean integral doses for the brainstem and skull critical structures when compared to that of TMR10 doses, these results were not statistically or clinically significant. Thus we continue to use the TMR10 algorithm at our clinic.
THE VIRTUE OF RUNNING A MARATHON
Authors: Gozzano Simone
Published: June 2019

Running a marathon is not solely a personal achievement; rather it sets an example. Because of the nature of this example, it constitutes an achievement that deserves our praise (contrary to what has recently been argued in this Journal).
HOW TO THINK ABOUT THE GUN CONTROL DEBATE
Authors: Hsiao Timothy
Published: June 2019

Many on both sides of the gun control debate are under the impression that the best way to settle it is by weighing outcomes in the context of a utilitarian cost-benefit analysis. This article suggests that this way of thinking about the gun control debate is fundamentally mistaken. What matters is not therisk(or lack thereof) that guns pose to society, but simply whether guns are areasonable means of self-defencewhen used to resist crimes. What this means is that even if we were to grant the claim that gun ownership decreases average safety, it wouldn't follow that restrictive gun control measures would be justified.
“I’m Not the President of Black America”: Rhetorical versus Policy Representation
Authors: Haines Pavielle E. , Mendelberg Tali , Butler Bennett
Published: June 2019

A key question in the study of minority representation is whether descriptive representatives provide superior substantive representation. Neglected in this literature is the distinction between two forms of substantive representation: rhetoric versus policy. We provide a systematic comparison of presidential minority representation along these two dimensions. Barack Obama was the first African American president, yet his substantive representation of African Americans has not been fully evaluated. Using speech and budget data, we find that relative to comparable presidents, Obama offered weaker rhetorical representation, but stronger policy representation, on race and poverty. While we cannot rule out non-racial explanations, Obama’s policy proposals are consistent with minority representation. His actions also suggest that descriptive representatives may provide relatively better policy representation but worse rhetorical representation, at least when the constituency is a numerical minority. We thus highlight an understudied tension between rhetoric and policy in theories of minority representation.
Effects of Lycopene in Hyperoxia-Induced Lung Injury in Newborn Rats
Authors: Bastug Osman , Fatih Sonmez Mehmet , Ozturk Mehmet Adnan , Korkmaz Levent , Kesici Hakan , Cilenk Kubra Tugce , Halis Hulya , Korkut Sabriye , Ozdemir Ahmet , Bastug Funda , Gunes Tamer , Kurtoglu Selim
Published: June 2019

Abstract. The aim of this study was to evaluate the therapeutic effect of lycopene on a hyperoxia-induced lung injury model in rat pups. Full-term rat pups were included in the study 12–24 h after delivery. The pups were separated into 4 groups: normoxia control (NC), hyperoxia control (HC), hyperoxia + lycopene (HL), and normoxia lycopene (NL). The normoxia groups were housed in ambient air, and the hyperoxia groups in > 85% O2. HL and NL groups received 50 mg lycopene in oil/kg body weight/day delivered intraperitoneally (i.p.), the other groups received oil alone. On day 11, the rat pups were sacrificed and their lungs removed. Statistically significant injury was observed in all histological parameters measured (MLI, proliferating cell nuclear antigen (PCNA), and apoptosis) in the HC group (HC vs NC, p = 0.001). This injury could not be reversed with lycopene treatment (HC vs HL, 0.05; NC vs HL, p = 0.001). With hyperoxia, statistically significant decreases were observed in biochemical parameters in terms of SOD, MDA, and IL-6 values (HC vs NC: SOD, p = 0.02; MDA, p = 0.043; IL-6, p = 0.001). The use of lycopene did not provide any improvement in these values (HC vs HL, p > 0.05). Hyperoxia or lycopene had no effect on IL-1β and GPx (p > 0.05). When comparing NC and NL groups, negative effects were observed in the group given lycopene in terms of MLI, PCNA, apoptosis, and IL-6 (all parameters, p = 0.001). We observed that 50 mg lycopene in oil/kg body weight/day given via i.p. had no curative effect on the hyperoxia-induced lung injury in newborn rats and may even induce adverse effects.
The Consumption of Breakfast, Fish and/or Caffeine does not Predict	Study Progress in Adult Distance Education
Authors: Gijselaers Hieronymus J.M. , Kirschner Paul A. , de Groot Renate H.M.
Published: June 2019

Abstract. Consumption of breakfast, fish, or caffeine are each separately often investigated in relation to learning performance in traditional education, but not in distance education (DE). The objective of this study was to investigate whether the relations between the consumption of breakfast, fish, and/or caffeine on the one hand and learning performance on the other are also found in DE students. This population is different from traditional students and characterized by a different profile in terms of age, personal and work responsibilities as well as other demographics. In an observational longitudinal study, the consumption of breakfast, fish, and caffeine of 1157 DE students (18–76 years old, mean 35.8 ± 11.1 years) was used to predict learning performance using multiple regression analysis. In an online digital survey, university students provided information about their consumption of these nutritional measures and on important covariates. Learning performance, measured as study progress (i.e., the number of successfully completed modules), was evaluated objectively after 14 months. Results showed that adding the consumption of breakfast, fish, and caffeine to the covariate model did not fit the data better, χ2 (3, N = 1155) = 3.287, p = 0.35. This means that neither the consumption of breakfast nor fish nor caffeine predicted study progress in adults participating in DE. This study is important as it is the first to report on these relations in this specific age group and educational setting, which is increasingly important due to the increased preference for this type of education.
Regulation of Spatial Changes in Phytoplankton Community by Water Column Stability and Nutrients in the Southern Yellow Sea
Authors: Jiang Zhibing , Chen Jianfang , Gao Yuexin , Zhai Hongchang , Jin Haiyan , Zhou Feng , Shou Lu , Yan Xiaojun , Chen Quanzhen
Published: June 2019

The southern Yellow Sea (SYS) shows extensive spatial variations in water masses, particularly YS Warm Current Water (YSWCW) and YS Coastal Current Water in cold and YS Bottom Cold Water (YSBCW) and Changjiang Diluted Water in warm seasons. These hydrographic processes result in significant spatial changes in nutrients, stratification, and turbidity, which may highly regulate phytoplankton distribution in the SYS. Here, we provide high spatial resolution data sets of phytoplankton in the SYS in all seasons during 2011–2012. Diatoms thrived in eutrophic Changjiang Diluted Water and YS Coastal Current Water regions. Notably, benthic/meroplanktonic diatoms, including Paralia sulcata and Rhaphoneis spp., were dominant near the Changjiang Estuary and Subei Shoal. However, cryptophytes and haptophytes were dominant in oligotrophic offshore regions controlled by YSWCW and YSBCW. Phytoplankton abundance and chlorophyll a were considerably lower in the YSWCW and YSBCW than in other regions, and the community composition varied significantly among regions. Algal blooms were observed off the SYS coast in spring and near the Changjiang Estuary in summer, which were characterized by abundant nutrients, low turbidity, and a relatively stable water column. Canonical correspondence analysis demonstrated that stratification in cold and nutrients in warm seasons were most important variables correlated with phytoplankton community. Variation partitioning analysis confirmed that spatial changes in phytoplankton community composition were largely structured by nutrients rather than by physical factors in all seasons except winter. Our findings highlight the significance of water column stability and nutrients associated with water mass variation in shaping spatial changes of phytoplankton community in the SYS.
Steve: The Optical Signature of Intense Subauroral Ion Drifts
Authors: Archer W. E. , Gallardo‐Lacourt B. , Perry G. W. , St.‐Maurice J. P. , Buchert S. C. , Donovan E.
Published: June 2019

Little is currently known about the optical phenomenon known as Steve. The first scientific publication on the subject suggests that Steve is associated with an intense subauroral ion drift (SAID). However, additional inquiry is warranted as this suggested relationship as it is based on a single case study. Here we present eight occurrences of Steve with coincident or near‐coincident measurements from the European Space Agency's Swarm satellites and show that Steve is consistently associated with SAID. When satellite observations coincident with Steve are compared to that of typical SAID, we find the SAID associated with Steve to have above average peak ion velocities and electron temperatures, as well as extremely low plasma densities.
The Error in Using Superposition to Estimate Pressure During Multisite Subsurface CO2Storage
Authors: De Simone Silvia , Jackson Samuel J. , Krevor Samuel
Published: June 2019

Analytic pressure estimates for multisite CO2injection are typically performed through the superposition of single‐site injection models. This is theoretically invalid for multiphase flow because of its nonlinearity. We quantify the error associated with the application of superposition in scenarios with sites located in a rectangular grid geometry. We show that the use of superposition results in overestimates of the pressure buildup, because it neglects the presence of multiple CO2plumes, which increase the reservoir fluid mobility. The adoption of a dimensionless time scaled to the geometric average between the advective and diffusive characteristic times allows us to define a general model for the maximum error, which may be used to evaluate the validity of using superposition, or to correct the pressure estimates when errors are significant. This procedure can be applied to any analytical solution and advances the extension of single‐well models to scenarios of multiple injection sites.
Widespread Fault Creep in the Northern San Francisco Bay Area Revealed by Multistation Cluster Detection of Repeating Earthquakes
Authors: Shakibay Senobari Nader , Funning Gareth J.
Published: June 2019

We search for repeating earthquakes (REs) in the northern San Francisco Bay Area in 1984–2016. By comparing over 670,000 waveforms from ∼75,000 events, we identify candidate clusters of events whose waveforms have high cross‐correlation coefficients at multiple stations. A key difference with our approach is that these “multistation clusters” do not require each event in a family be recorded at multiple common stations. We validate these candidate REs by estimating precise relative relocations for the events in each cluster. We identify 59 RE families whose relocated hypocenters are separated by less than one source radius. These are distributed throughout the Maacama fault zone and along the northern Rodgers Creek and central Bartlett Springs faults, implying that widespread, pervasive creep occurs on those faults, at rates of 1–6 mm/year. At either end of the Maacama fault, the RE pattern highlights structural complexity, suggesting that multiple subparallel strands may be active and creeping.
Improved Earth Oblateness Rate Reveals Increased Ice Sheet Losses and Mass‐Driven Sea Level Rise
Authors: Loomis B. D. , Rachlin K. E. , Luthcke S. B.
Published: June 2019

Satellite laser ranging (SLR) observations are routinely applied toward the estimation of dynamic oblateness, C20, which is the largest globally integrated component of Earth's time‐variable gravity field. Since 2002, GRACE and GRACE Follow‐On have revolutionized the recovery of higher spatial resolution features of global time‐variable gravity, with SLR continuing to provide the most reliable estimates of C20. We quantify the effect of various SLR processing strategies on estimating C20 and demonstrate better signal recovery with the inclusion of GRACE‐derived low‐degree gravity information in the forward model. This improved SLR product modifies the Antarctic and Greenland Ice Sheet mass trends by −15.4 and −3.5 Gt/year, respectively, as compared to CSR TN11, and improves global mean sea level budget closure by modifying sea level rise by +0.08 mm/year. We recommend that this new C20 product be applied to RL06 GRACE data products for enhanced accuracy and scientific interpretation.
Ionospheric Footprints of Detached Magnetotail Interchange Heads
Authors: Panov E. V. , Baumjohann W. , Nakamura R. , Pritchett P. L. , Weygand J. M. , Kubyshkina M. V.
Published: June 2019

Pritchett and Coroniti (2011, https://doi.org/10.1029/2011GL047527, 2013, https://doi.org/10.1029/2012JA018143) have predicted that the kinetic ballooning/interchange instability (BICI) can provoke reconnection onsets that lead to detached azimuthally thin earthward intrusions (heads) of depleted plasma tubes when
 100. Such detached BICI heads would be seen as localized earthward‐propagating dipolarization fronts. Using Time History of Events and Macroscale Interactions during Substorms observations in the plasma sheet at XGSM≈−11RE and conjugate All‐Sky Imager and magnetometer networks observations on the ground, we show four examples when prominent dipolarization fronts with moderate earthward flows were observed amidst azimuthally drifting interchange heads and concurrently with the ionospheric current intensifications near Time History of Events and Macroscale Interactions during Substorms footprints and auroral bright spots originating from dimmer azimuthal beads/rays. These events support the idea that some of the BICI heads detach from the region with reversed radial gradient of BZ due to local reconnection. The detached BICI heads propagate earthward‐driving ionospheric pseudo‐breakups.
Variations in Elastic and Electrical Properties of Crustal Rocks With Varying Degree of Microfracturation
Authors: Pimienta L. , Orellana L. F. , Violay M.
Published: June 2019

This work aims at investigating the effect of varying degrees of microfracturing on the joint elastic and electrical transport properties of rocks. Different crustal rocks were subjected to thermal treatment, expected to induce microfracturing, up to different target temperatures from 100 up to 900 °C. The rocks bulk and pore volumes, P and S wave velocities, and frequency‐dependent electrical impedance were measured before and after the treatment. As the temperature of treatment increased, P and S wave velocities and the electrical formation factor drop and pore and bulk volumes increase. As indicated by the microscopic images, this is consistent with the creation of microcracks. These created microcracks do not affect the properties in the exact same manner, and a strong effect of the initial porosity is observed for electrical formation factor. Extrapolating to low‐frequency field‐scale measurements in water‐saturated reservoir rocks highlights an interesting observation: Both seismic and electrical properties at the field scale might highlight similar variations with increasing damage in all rocks. The maximum amount of decrease expected for all rocks is about 1 order of magnitude in electrical formation factor and 40% decrease in P and S wave velocities. Finally, temperature proved to affect very differently the rocks of varying porosity and mineral content, in ways not fully covered by existing works. Porosity, by increasing the matrix compressibility, damps the degree of microfracturing and crack opening. The distinct behavior in calcite‐pure marble evidences a dominance of anisotropic of thermal expansion over isotropic expansion mismatch.
Impact of Chemical Environment on Compaction Creep of Quartz Sand and Possible Geomechanical Applications
Authors: Schimmel M. T. W. , Hangx S. J. T. , Spiers C. J.
Published: June 2019

Induced seismicity and surface subsidence are adverse effects of natural gas and geothermal energy production that may present barriers to their use as low‐carbon alternatives to coal and oil. The driving force for these unwanted effects is compaction of the reservoir, which can potentially be mitigated by injecting (pressurized) fluids that restore the pore pressure and chemically inhibit compaction. We conducted uniaxial compaction experiments on quartz sand aggregates to investigate the effect of pore fluid chemistry on time‐dependent compaction (creep). In addition to a low‐vacuum (dry) environment, supercritical fluids (N2, CO2, and wet CO2), simple aqueous solutions (three HCl solutions and a NaOH solution), and complex aqueous solutions with additives (AlCl3, AMP, and washing detergent) were employed. N2, CO2, and fluids containing scaling inhibitor (AMP), as well as wastewater (detergent solution) are generally considered for injection. Compaction creep was enhanced in fluid‐saturated environments compared to dry. Wet CO2 caused more creep with faster strain rates than the relatively dry CO2 and N2 environments. Experiments conducted with simple aqueous solutions exhibited a clear pH dependency. The complex aqueous solutions enhanced creep compared to their simple solution counterpart with similar pH. Based on acoustic emission data and microstructural analyses, we inferred that compaction creep was controlled by subcritical crack growth, aided by water, hydroxyl ions, and additives. If microcracking also controls compaction in reservoir sandstones, these results indicate that injection of supercritical fluids or acidic solutions may mitigate reservoir compaction.
The Max Planck Institute Grand Ensemble: Enabling the Exploration of Climate System Variability
Authors: Maher Nicola , Milinski Sebastian , Suarez‐Gutierrez Laura , Botzet Michael , Dobrynin Mikhail , Kornblueh Luis , Kröger Jürgen , Takano Yohei , Ghosh Rohit , Hedemann Christopher , Li Chao , Li Hongmei , Manzini Elisa , Notz Dirk , Putrasahan Dian , Boysen Lena , Claussen Martin , Ilyina Tatiana , Olonscheck Dirk , Raddatz Thomas , Stevens Bjorn , Marotzke Jochem
Published: June 2019

The Max Planck Institute Grand Ensemble (MPI‐GE) is the largest ensemble of a single comprehensive climate model currently available, with 100 members for the historical simulations (1850–2005) and four forcing scenarios. It is currently the only large ensemble available that includes scenario representative concentration pathway (RCP) 2.6 and a 1% CO2 scenario. These advantages make MPI‐GE a powerful tool. We present an overview of MPI‐GE, its components, and detail the experiments completed. We demonstrate how to separate the forced response from internal variability in a large ensemble. This separation allows the quantification of both the forced signal under climate change and the internal variability to unprecedented precision. We then demonstrate multiple ways to evaluate MPI‐GE and put observations in the context of a large ensemble, including a novel approach for comparing model internal variability with estimated observed variability. Finally, we present four novel analyses, which can only be completed using a large ensemble. First, we address whether temperature and precipitation have a pathway dependence using the forcing scenarios. Second, the forced signal of the highly noisy atmospheric circulation is computed, and different drivers are identified to be important for the North Pacific and North Atlantic regions. Third, we use the ensemble dimension to investigate the time dependency of Atlantic Meridional Overturning Circulation variability changes under global warming. Last, sea level pressure is used as an example to demonstrate how MPI‐GE can be utilized to estimate the ensemble size needed for a given scientific problem and provide insights for future ensemble projects.
Validation of the animal model of bipolar disorder induced by Ouabain: face, construct and predictive perspectives
Authors: Valvassori Samira S. , Dal-Pont Gustavo C. , Resende Wilson R. , Varela Roger B. , Lopes-Borges Jéssica , Cararo José Henrique , Quevedo João
Published: June 2019

A particular challenge in the development of a bipolar disorder (BD) model in animals is the complicated clinical course of the condition, characterized by manic, depressive and mixed mood episodes. Ouabain (OUA) is an inhibitor of Na+/K+-ATPase enzyme. Intracerebroventricular (ICV) injection of this drug in rats has been regarded a proper model to study BD by mimic specific manic symptoms, which are reversed by lithium (Li), an important mood stabilizer drug. However, further validation of this experimental approach is required to characterize it as an animal model of BD, including depressive-like behaviors. The present study aimed to assess manic- and depressive-like behaviors, potential alteration in the hypothalamic-pituitary-adrenal (HPA) system and oxidative stress parameters after a single OUA ICV administration in adult male Wistar rats. Moreover, we evaluated Li effects in this experimental setting. Data show that OUA ICV administration could constitute a suitable model for BD since the injection of the drug triggered manic- and depressive-like behaviors in the same animal. Additionally, the OUA model mimics significant physiological and neurochemical alterations detected in BD patients, including an increase in oxidative stress and change in HPA axis. Our findings suggest that decreased Na+/K+-ATPase activity detected in bipolar patients may be linked to increased secretion of glucocorticoid hormones and oxidative damage, leading to the marked behavioral swings. The Li administration mitigated these pathological changes in the rats. The proposed OUA model is regarded as suitable to simulate BD by complying with all validities required to a proper animal model of the psychiatric disorder.
The roles and mechanism of IFIT5 in bladder cancer epithelial–mesenchymal transition and progression
Authors: Huang Jun , Lo U-Ging , Wu Shiqi , Wang Bin , Pong Rey-Chen , Lai Chih-Ho , Lin Ho , He Dalin , Hsieh Jer-Tsong , Wu Kaijie
Published: June 2019

The prognosis of bladder cancer (BCa) depends on several key factors including anatomical site, tumor grade, and stage. In general, muscle-invasive bladder cancer (MIBC) is associated with higher incidence of distant metastasis compared with Non-muscle-invasive bladder cancer (NMIBC). Treatment outcome of the patients with metastatic BCa has been very poor with ~15% of overall survival rate. Thus, it is apparently important to understand the underlying biology for metastatic progression of BCa. Although epithelial–mesenchymal transition (EMT) has long been implicated in BCa metastasis and treatment resistance, the underlying mechanism is not fully understood. In this study, we have identified that the expression of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is positively correlated with pathological characteristics, and predicts a poor prognosis of BCa patients. Since the function of IFIT5 in BCa has not yet been characterized, we demonstrate that IFIT5 can induce EMT, promote cell migration and invasion, and increase the expression of ICAM1 in BCa via down-regulation of mature miR-99a. Moreover, ICAM1 is shown as a direct target of miR-99a. Overall, we conclude that IFIT5 is a new oncogene in BCa.
Relationship between rheology and structure of interpenetrating, deforming and compressing microgels
Authors: Conley Gaurasundar M. , Zhang Chi , Aebischer Philippe , Harden James L. , Scheffold Frank
Published: June 2019

Thermosensitive microgels are widely studied hybrid systems combining properties of polymers and colloidal particles in a unique way. Due to their complex morphology, their interactions and packing, and consequentially the viscoelasticity of suspensions made from microgels, are still not fully understood, in particular under dense packing conditions. Here we study the frequency-dependent linear viscoelastic properties of dense suspensions of micron sized soft particles in conjunction with an analysis of the local particle structure and morphology based on superresolution microscopy. By identifying the dominating mechanisms that control the elastic and dissipative response, we can explain the rheology of these widely studied soft particle assemblies from the onset of elasticity deep into the overpacked regime. Interestingly, our results suggest that the friction between the microgels is reduced due to lubrification mediated by the polymer brush-like corona before the onset of interpenetration.
Quantifying and predicting success in show business
Authors: Williams Oliver E. , Lacasa Lucas , Latora Vito
Published: June 2019

In certain artistic endeavours—such as acting in films and TV, where unemployment rates hover at around 90%—sustained productivity (simply making a living) is probably a better proxy for quantifying success than high impact. Drawing on a worldwide database, here we study the temporal profiles of activity of actors and actresses. We show that the dynamics of job assignment is well described by a “rich-get-richer” mechanism and we find that, while the percentage of a career spent active is unpredictable, such activity is clustered. Moreover, productivity tends to be higher towards the beginning of a career and there are signals preceding the most productive year. Accordingly, we propose a machine learning method which predicts with 85% accuracy whether this “annus mirabilis” has passed, or if better days are still to come. We analyse actors and actresses separately, also providing compelling evidence of gender bias in show business.
Aβ-induced vulnerability propagates via the brain’s default mode network
Authors: Pascoal Tharick A. , Mathotaarachchi Sulantha , Kang Min Su , Mohaddes Sara , Shin Monica , Park Ah Yeon , Parent Maxime J. , Benedet Andrea L. , Chamoun Mira , Therriault Joseph , Hwang Heungsun , Cuello A. Claudio , Misic Bratislav , Soucy Jean-Paul , Aston John A. D. , Gauthier Serge , Rosa-Neto Pedro
Published: June 2019

The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer’s disease. Here, using positron emission tomography ([18F]florbetapir tracer for Aβ and [18F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aβ aggregation within the brain’s default mode network leads to regional hypometabolism in distant but functionally connected brain regions. Moreover, we found that an interaction between this hypometabolism with overlapping Aβ aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aβ rats that do not form neurofibrillary tangles, which support these findings as an independent mechanism of cognitive deterioration. These results suggest a model in which distant Aβ induces regional metabolic vulnerability, whereas the interaction between local Aβ with a vulnerable environment drives the clinical progression of dementia.
Tunable self-healing of magnetically propelling colloidal carpets
Authors: Massana-Cid Helena , Meng Fanlong , Matsunaga Daiki , Golestanian Ramin , Tierno Pietro
Published: June 2019

The process of crystallization is difficult to observe for transported, out-of-equilibrium systems, as the continuous energy injection increases activity and competes with ordering. In emerging fields such as microfluidics and active matter, the formation of long-range order is often frustrated by the presence of hydrodynamics. Here we show that a population of colloidal rollers assembled by magnetic fields into large-scale propelling carpets can form perfect crystalline materials upon suitable balance between magnetism and hydrodynamics. We demonstrate a field-tunable annealing protocol based on a controlled colloidal flow above the carpet that enables complete crystallization after a few seconds of propulsion. The structural transition from a disordered to a crystalline carpet phase is captured via spatial and temporal correlation functions. Our findings unveil a novel pathway to magnetically anneal clusters of propelling particles, bridging driven systems with crystallization and freezing in material science.
Chemically modified graphene films with tunable negative Poisson’s ratios
Authors: Wen Yeye , Gao Enlai , Hu Zhenxing , Xu Tingge , Lu Hongbing , Xu Zhiping , Li Chun
Published: June 2019

Graphene-derived macroscopic assemblies feature hierarchical nano- and microstructures that provide numerous routes for surface and interfacial functionalization achieving unconventional material properties. We report that the microstructural hierarchy of pristine chemically modified graphene films, featuring wrinkles, delamination of close-packed laminates, their ordered and disordered stacks, renders remarkable negative Poisson’s ratios ranging from −0.25 to −0.55. The mechanism proposed is validated by the experimental characterization and theoretical analysis. Based on the understanding of microstructural origins, pre-strech is applied to endow chemically modified graphene films with controlled negative Poisson’s ratios. Modulating the wavy textures of the inter-connected network of close-packed laminates in the chemically modified graphene films also yields finely-tuned negative Poisson’s ratios. These findings offer the key insights into rational design of films constructed from two-dimensional materials with negative Poisson’s ratios and mechanomutable performance.
A synthesis strategy for tetracyclic terpenoids leads to agonists of ERβ
Authors: Kim Wan Shin , Shalit Zachary A. , Nguyen Sidney M. , Schoepke Emmalie , Eastman Alan , Burris Thomas P. , Gaur Arti B. , Micalizio Glenn C.
Published: June 2019

Natural product and natural product-like molecules continue to be important for the development of pharmaceutical agents, as molecules in this class play a vital role in the pipeline for new therapeutics. Among these, tetracyclic terpenoids are privileged, with >100 being FDA-approved drugs. Despite this significant pharmaceutical success, there remain considerable limitations to broad medicinal exploitation of the class due to lingering scientific challenges associated with compound availability. Here, we report a concise asymmetric route to forging natural and unnatural (enantiomeric) C19 and C20 tetracyclic terpenoid skeletons suitable to drive medicinal exploration. While efforts have been focused on establishing the chemical science, early investigations reveal that the emerging chemical technology can deliver compositions of matter that are potent and selective agonists of the estrogen receptor beta, and that are selectively cytotoxic in two different glioblastoma cell lines (U251 and U87).
CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer
Authors: Racioppi Luigi , Nelson Erik R. , Huang Wei , Mukherjee Debarati , Lawrence Scott A. , Lento William , Masci Anna Maria , Jiao Yiquin , Park Sunghee , York Brian , Liu Yaping , Baek Amy E. , Drewry David H. , Zuercher William J. , Bertani Francesca R. , Businaro Luca , Geradts Joseph , Hall Allison , Means Anthony R. , Chao Nelson , Chang Ching-yi , McDonnell Donald P.
Published: June 2019

Tumor-associated myeloid cells regulate tumor growth and metastasis, and their accumulation is a negative prognostic factor for breast cancer. Here we find calcium/calmodulin-dependent kinase kinase (CaMKK2) to be highly expressed within intratumoral myeloid cells in mouse models of breast cancer, and demonstrate that its inhibition within myeloid cells suppresses tumor growth by increasing intratumoral accumulation of effector CD8+ T cells and immune-stimulatory myeloid subsets. Tumor-associated macrophages (TAMs) isolated from Camkk2−/− mice expressed higher levels of chemokines involved in the recruitment of effector T cells compared to WT. Similarly, in vitro generated Camkk2−/− macrophages recruit more T cells, and have a reduced capability to suppress T cell proliferation, compared to WT. Treatment with CaMKK2 inhibitors blocks tumor growth in a CD8+ T cell-dependent manner, and facilitates a favorable reprogramming of the immune cell microenvironment. These data, credential CaMKK2 as a myeloid-selective checkpoint, the inhibition of which may have utility in the immunotherapy of breast cancer.
Invariance properties of bacterial random walks in complex structures
Authors: Frangipane Giacomo , Vizsnyiczai Gaszton , Maggi Claudio , Savo Romolo , Sciortino Alfredo , Gigan Sylvain , Di Leonardo Roberto
Published: June 2019

Motile cells often explore natural environments characterized by a high degree of structural complexity. Moreover cell motility is also intrinsically noisy due to spontaneous random reorientations and speed fluctuations. This interplay of internal and external noise sources gives rise to a complex dynamical behavior that can be strongly sensitive to details and hard to model quantitatively. In striking contrast to this general picture we show that the mean residence time of swimming bacteria inside artificial complex microstructures is quantitatively predicted by a generic invariance property of random walks. We find that while external shape and internal disorder have dramatic effects on the distributions of path lengths and residence times, the corresponding mean values are constrained by the sole free surface to perimeter ratio. As a counterintuitive consequence, bacteria escape faster from structures with higher density of obstacles due to the lower accessible surface.
Remediation of heavy metal contaminated soil by asymmetrical alternating current electrochemistry
Authors: Xu Jinwei , Liu Chong , Hsu Po-Chun , Zhao Jie , Wu Tong , Tang Jing , Liu Kai , Cui Yi
Published: June 2019

Soil contamination by heavy metals constitutes an important environmental problem, whereas field applicability of existing remediation technologies has encountered numerous obstacles, such as long operation time, high chemical cost, large energy consumption, secondary pollution, and soil degradation. Here we report the design and demonstration of a remediation method based on a concept of asymmetrical alternating current electrochemistry that achieves high degrees of contaminant removal for different heavy metals (copper, lead, cadmium) at different initial concentrations (from 100 to 10,000 ppm), all reaching corresponding regulation levels for residential scenario after rational treatment time (from 30 min to 6 h). No excessive nutrient loss in treated soil is observed and no secondary toxic product is produced. Long-term experiment and plant assay show the high sustainability of the method and its feasibility for agricultural use.
Author Correction: Efficient electron transfer across hydrogen bond interfaces by proton-coupled and -uncoupled pathways
Authors: Cheng Tao , Shen Dong Xue , Meng Miao , Mallick Suman , Cao Lijiu , Patmore Nathan J. , Zhang Hong Li , Zou Shan Feng , Chen Huo Wen , Qin Yi , Wu Yi Yang , Liu Chun Y.
Published: June 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Transparent conducting materials discovery using high-throughput computing
Authors: Brunin Guillaume , Ricci Francesco , Ha Viet-Anh , Rignanese Gian-Marco , Hautier Geoffroy
Published: June 2019

Transparent conducting materials (TCMs) are required in many applications from solar cells to transparent electronics. Developing high performance materials combining the antagonistic properties of transparency and conductivity has been challenging especially for p-type materials. Recently, high-throughput ab initio computational screening has emerged as a formidable tool for accelerating materials discovery. In this review, we discuss how this approach has been applied for identifying TCMs. We provide a brief overview of the different materials properties of importance for TCMs (e.g., dopability, effective mass, and transparency) and present the ab initio techniques available to assess them. We focus on the accuracy of the methodologies as well as their suitability for high-throughput computing. Finally, we review the different high-throughput computational studies searching for new TCMs and discuss their differences in terms of methodologies and main findings.
Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice
Authors: Bokhari Rihana S. , Metzger Corinne E. , Black Jeremy M. , Franklin Katherine A. , Boudreaux Ramon D. , Allen Matthew R. , Macias Brandon R. , Hogan Harry A. , Braby Leslie A. , Bloomfield Susan A.
Published: June 2019

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56Fe or sham (n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56Fe exposure resulted in 65–78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values.
Establishment and genomic characterization of gingivobuccal carcinoma cell lines with smokeless tobacco associated genetic alterations and oncogenic PIK3CA mutation
Authors: Pansare Kshama , Gardi Nilesh , Kamat Sayee , Dange Prerana , Previn Rahul , Gera Poonam , Kowtal Pradnya , Amin Kishore , Sarin Rajiv
Published: June 2019

Smokeless tobacco associated Gingivobuccal squamous cell carcinoma (GB-SCC) is a major public health problem but available oral cancer cell lines are mostly from smoking associated tongue SCC raising the need for pertinent GB-SCC cell line models. As part of the International Cancer Genome Consortium (ICGC) Project, 4 novel cell lines, namely, Indian Tata Memorial Centre Oral Cancer (ITOC) −01 to −04 were established and characterized with conventional methods, karyotyping, ultrastructure, in vivo tumourigenicity, Whole exome sequencing (WES) and RNA sequencing. These hyperploid cell lines form xenografts in mice and show metabolically active and necrotic areas on fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. WES of ITOC cell lines recapitulate the genomic tumor profile of ICGC GB-SCC database. We further identified smokeless tobacco associated genetic alterations (PCLO, FAT3 and SYNE2) and oncogenic PIK3CA mutation in GB-SCC cell lines. Transcriptome profiling identified deregulation of pathways commonly altered in cancer and down-regulation of arachidonic acid metabolism pathway, implying its possible role in GB-SCC. Clinical application of high throughput sequencing data depends on relevant cell line models to validate potential targets. Extensively characterized, these oral SCC cell lines are particularly suited for mechanistic studies and pre-clinical drug development for smokeless tobacco associated oral cancer.
Highly polarized photoluminescence from c-plane InGaN/GaN multiple quantum wells on stripe-shaped cavity-engineered sapphire substrate
Authors: Kim Jongmyeong , Lee Seungmin , Oh Jehong , Ryu Jungel , Park Yongjo , Park Seoung-Hwan , Yoon Euijoon
Published: June 2019

Highly polarized photoluminescence (PL) from c-plane InGaN/GaN multiple quantum wells (MQWs) grown on stripe-shaped cavity-engineered sapphire substrate (SCES) was realized. The polarization ratio was as high as 0.74 at room temperature. High-resolution X-ray reciprocal space mapping measurements revealed that the InGaN quantum wells on GaN/SCES template were under considerable anisotropic in-plane strain states of −1.178% and −1.921% along the directions perpendicular and parallel to the stripe-pattern, respectively. The anisotropic strain states were attributed to the anisotropic alignment of cavity-incorporated sapphire nano-membranes, which accommodated both anisotropic elastic relaxation in the InGaN quantum well plane as well as the graded elastic relaxation along the vertical direction in the GaN template adjacent to the InGaN/GaN MQWs. The partial strain relaxation in the InGaN wells also contributed to reduction of quantum confined Stark effect, resulting in four times higher PL intensity than InGaN/GaN MQWs on planar sapphire substrate. From theoretical calculations based on k∙p perturbation theory, it was found that fundamental origin of the polarized optical emission was strain-induced modification of valence band structures of the InGaN/GaN MQWs on the SCES. This study will allow us to realize light emitting diodes with highly polarized emission with conventional c-plane sapphire substrates by strain-induced valence band modification.
Alcohol consumption is associated with the risk of developing colorectal neoplasia: Propensity score matching analysis
Authors: Yang Young Joo , Bang Chang Seok , Choi Jae Ho , Lee Jae Jun , Shin Suk Pyo , Suk Ki Tae , Baik Gwang Ho , Kim Dong Joon
Published: June 2019

Although alcohol intake is known to be associated with the development of colorectal cancer, the effect of alcohol consumption on the development of colorectal neoplasm (CRN) is unclear. We performed a retrospective cohort analysis with 1 to 1 propensity score matching in a single center of Korea. Among 1,448 patients who underwent index and surveillance colonoscopy, 210 matched pairs were analyzed. The 5-year cumulative occurrence of overall CRN after index colonoscopy was higher in the significant alcohol consumption group (defined as alcohol consumption more than 30 g/day in men and 20 g/day in women) (vs. without significant alcohol consumption group) (40% vs. 27.6%, p = 0.004). Significant alcohol consumption increased the development of overall CRN (adjusted hazard ratio [aHR]: 1.86, 95% confidence interval [CI]: 1.28–2.70, p = 0.001) at surveillance colonoscopy. However, this effect was not valid on the development of advanced CRN. In subgroup analysis considering the risk classification of index colonoscopy, significant alcohol consumption increased the overall CRN development at surveillance colonoscopy in the normal group (patients with no detected adenoma in the index colonoscopy) (aHR: 1.90, 95% CI: 1.16–3.13, p = 0.01). Alcohol consumption habits should be considered in optimizing time intervals of surveillance colonoscopy.
Monozygotic twins and triplets discordant for amyotrophic lateral sclerosis display differential methylation and gene expression
Authors: Tarr Ingrid S. , McCann Emily P. , Benyamin Beben , Peters Timothy J. , Twine Natalie A. , Zhang Katharine Y. , Zhao Qiongyi , Zhang Zong-Hong , Rowe Dominic B. , Nicholson Garth A. , Bauer Denis , Clark Susan J. , Blair Ian P. , Williams Kelly L.
Published: June 2019

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of upper and lower motor neurons. ALS exhibits high phenotypic variability including age and site of onset, and disease duration. To uncover epigenetic and transcriptomic factors that may modify an ALS phenotype, we used a cohort of Australian monozygotic twins (n = 3 pairs) and triplets (n = 1 set) that are discordant for ALS and represent sporadic ALS and the two most common types of familial ALS, linked to C9orf72 and SOD1. Illumina Infinium HumanMethylation450K BeadChip, EpiTYPER and RNA-Seq analyses in these ALS-discordant twins/triplets and control twins (n = 2 pairs), implicated genes with consistent longitudinal differential DNA methylation and/or gene expression. Two identified genes, RAD9B and C8orf46, showed significant differential methylation in an extended cohort of >1000 ALS cases and controls. Combined longitudinal methylation-transcription analysis within a single twin set implicated CCNF, DPP6, RAMP3, and CCS, which have been previously associated with ALS. Longitudinal transcriptome data showed an 8-fold enrichment of immune function genes and under-representation of transcription and protein modification genes in ALS. Examination of these changes in a large Australian sporadic ALS cohort suggest a broader role in ALS. Furthermore, we observe that increased methylation age is a signature of ALS in older patients.
Petroleum as source and carrier of metals in epigenetic sediment-hosted mineralization
Authors: Saintilan Nicolas J. , Spangenberg Jorge E. , Chiaradia Massimo , Chelle-Michou Cyril , Stephens Michael B. , Fontboté Lluís
Published: June 2019

Sediment-hosted ore deposits contribute a significant amount (up to 65%) of the global resources of lead and zinc. Among them, the Mississippi-Valley type deposits and related oil fields often comprise large-scale hydrothermal systems where regional host rocks are stained with disseminated liquid petroleum (crude oil) and other organic compounds. Current models for the formation of those epigenetic Pb-Zn sulphide deposits consider that metals are mostly leached from basement rocks and their detrital erosional products, and transported by oxidized basinal hydrothermal fluids as chloride complexes. Sulphide precipitation mainly occurs when these basinal brines interact with fluids rich in reduced sulphur species produced mostly by thermochemical sulphate reduction (TSR) mediated by hydrocarbons. Here, using organic geochemistry and Pb isotopes, we provide evidence that petroleum and associated water were key for the formation of sulphide mineralization in the world-class sandstone-hosted ore deposit at Laisvall, not only by supplying reduced sulphur but also by contributing metals in significant amounts. The lead originally found in bitumen of the Alum Shale Formation was transported —during an arc-continent collisional event— by liquid petroleum and associated water to the site of sulphide mineralization. The alteration of petroleum by TSR made lead available for precipitation as sulphide. The petroleum-associated lead represents 40 to 60% of the metal budget in the deposit, the remainder being sourced by leaching of basement rocks.