bluuebunny/crossref_metadata_2025 huggingface dataset:
On the stochastic dynamics of a nonlinear vibration energy harvester driven by Lévy flight excitations
Authors: RAMAKRISHNAN SUBRAMANIAN , EDLUND CONNOR , LAMBRECHT COLLIN
Published: October 2018

Vibration energy harvesting aims to harness the energy of ambient random vibrations for power generation, particularly in small-scale devices. Typically, stochastic excitation driving the harvester is modelled as a Brownian process and the dynamics are studied in the equilibrium state. However, non-Brownian excitations are of interest, particularly in the nonequilibrium regime of the dynamics. In this work we study the nonequilibrium dynamics of a generic piezoelectric harvester driven by Brownian as well as (non-Brownian) Lévy flight excitation, both in the linear and the Duffing regimes. Both the monostable and the bistable cases of the Duffing regime are studied. The first set of results demonstrate that Lévy flight excitation results in higher expectation values of harvested power. In particular, it is shown that increasing the noise intensity leads to a significant increase in power output. It is also shown that a linearly coupled array of nonlinear harvesters yields improved power output for tailored values of coupling coefficients. The second set of results show that Lévy flight excitation fundamentally alters the bifurcation characteristics of the dynamics. Together, the results underscore the importance of non-Brownian excitation characterised by Lévy flight in vibration energy harvesting, both from a theoretical viewpoint and from the perspective of practical applications.
Determinants of low birth weight in the context of maternal nutrition education in urban informal settlements, Kenya
Authors: Nyamasege C. K. , Kimani-Murage E. W. , Wanjohi M. , Kaindi D. W. M. , Ma E. , Fukushige M. , Wagatsuma Y.
Published: October 2018

Inadequate knowledge in maternal nutrition is one of the determinants of low birth weight. However, little evidence is available on whether maternal nutrition counselling alone can influence birth weight among women from low socioeconomic households. This study assessed the effect of prenatal maternal nutritional counselling on birth weight and examined the related risk factors. A cluster randomized controlled trial was conducted to assess the effectiveness of home-based maternal nutritional counselling on nutritional outcomes, morbidity, breastfeeding, and infant feeding practices by the African Population and Health Research Center in two urban informal settlements of Nairobi. The intervention group received monthly antenatal and nutritional counselling from trained community health volunteers; meanwhile, the control group received routine antenatal care. A total of 1001 participants were included for analysis. Logistic regression was applied to determine associations between low birth weight and maternal characteristics. A higher prevalence of low birth weight was observed in the control group (6.7%) than in the intervention group (2.5%; P<0.001). Logistic regression identified significant associations between birth weight and intervention group (adjusted odds ratio (AOR)=0.26; 95% confidence interval (CI), 0.10–0.64); maternal height <154.5 cm (AOR=3.33; 95% CI, 1.01–10.96); last antenatal care visits at 1st or 2nd trimesters (AOR=9.48; 95% CI, 3.72–24.15); pre-term delivery (AOR=3.93; 95% CI, 1.93–7.98); maternal mid-upper arm circumference <23 cm (AOR=2.57; 95% CI, 1.15–5.78); and cesarean delivery (AOR=2.27; 95% CI, 1.04–4.94). Nutrition counselling during pregnancy reduced low birth weight and preterm births, which was determined by women of short stature, early stoppage of antenatal visit, and cesarean delivery.
Herbicide Programs Utilizing Halauxifen-Methyl for Glyphosate-Resistant Horseweed (Conyza canadensis) Control in Soybean
Authors: Zimmer Marcelo , Young Bryan G. , Johnson William G.
Published: October 2018

Evolution of glyphosate-resistant (GR) weeds, such as horseweed, presents major challenges in no-till soybean production systems. Effective GR horseweed control with preplant burndown applications is necessary to prevent potential soybean yield losses due to competition and to manage the soil weed seedbank. Halauxifen-methyl is a new synthetic auxin herbicide for broadleaf weed control in preplant burndown applications for soybean and other crops at low use rates (5 g ae ha–1). Experiments were conducted to evaluate the efficacy of herbicide treatments containing halauxifen-methyl for control of GR horseweed in comparison to existing herbicide treatments utilized in no-till GR soybean systems. Glyphosate alone controlled horseweed 33%. Herbicide treatments that included halauxifen-methyl, dicamba, or saflufenacil in combination with glyphosate controlled horseweed 87% to 96%, 89%, and 93%, respectively, 35 d after burndown application (DAB). Horseweed control, horseweed density reduction, and ground cover reduction by halauxifen-methyl plus glyphosate was similar to dicamba plus glyphosate. Horseweed control was greater for halauxifen-methyl plus glyphosate than for 2,4-D plus glyphosate. Cloransulam, cloransulam plus flumioxazin, and cloransulam plus sulfentrazone added to halauxifen-methyl plus glyphosate increased horseweed control and reduced horseweed density. No herbicide injury or soybean yield reduction was observed for treatments containing halauxifen-methyl.
Holocene Surface Rupture History of an Active Forearc Fault Redefines Seismic Hazard in Southwestern British Columbia, Canada
Authors: Morell K. D. , Regalla C. , Amos C. , Bennett S. , Leonard L. , Graham A. , Reedy T. , Levson V. , Telka A.
Published: October 2018

Characterizing the hazard associated with Quaternary‐active faults in the forearc crust of the northern Cascadia subduction zone has proven challenging due to historically low rates of seismicity, late Quaternary glacial scouring, and dense vegetation that often obscures fault‐related geomorphic features. We couple lidar topography with paleoseismic trenching across the Leech River Fault on southern Vancouver Island to produce the first detailed surface rupture history of an onland forearc fault in British Columbia, Canada. The results indicate that this fault produced three surface‐rupturing earthquakes in the last ∼9 kyr and is therefore capable of producing large (Mw>6) earthquakes in the future. We provide new constraints on the fault's length (∼130 km) and Holocene slip rate (≥0.2–0.3 mm/year) that, together with the earthquake ages, should be incorporated into new seismic hazard assessments and building code practices relevant to urban centers in southwestern British Columbia (Canada) and northwestern Washington State (United States).
Retrievals of Arctic Sea‐Ice Volume and Its Trend Significantly Affected by Interannual Snow Variability
Authors: Bunzel Felix , Notz Dirk , Pedersen Leif Toudal
Published: October 2018

We estimate the uncertainty of satellite‐retrieved Arctic sea‐ice thickness, sea‐ice volume, and their trends stemming from the lack of reliable snow‐thickness observations. To do so, we simulate a Cryosat2‐type ice‐thickness retrieval in an ocean‐model simulation forced by atmospheric reanalysis, pretending that only freeboard is known as model output. We then convert freeboard to sea‐ice thickness using different snow climatologies and compare the resulting sea‐ice thickness retrievals to each other and to the real sea‐ice thickness of the reanalysis‐forced simulation. We find that different snow climatologies cause significant differences in the obtained ice thickness and ice volume. In addition, we show that Arctic ice‐volume trends derived from ice‐thickness retrievals using any snow‐depth climatology are highly unreliable because the estimated trend in ice volume can strongly be influenced by the neglected interannual variability in snow volume.
Reconciling Hadley Cell Expansion Trend Estimates in Reanalyses
Authors: Davis N. A. , Davis S. M.
Published: October 2018

Numerous studies have concluded that historical Hadley cell expansion simulated in reanalyses is much larger than the future expansion predicted by climate model simulations. Is Hadley cell expansion too weak in climate models, or are the trends in reanalyses spuriously large? This study shows that the mean meridional circulation in reanalyses generally does not conserve mass. The mass imbalance projects onto trends in the Hadley cell edge latitudes by modifying both the mean and anomalous circulation. In correcting for the imbalance, the majority of Hadley cell expansion trends in early‐generation reanalyses in both hemispheres are revised to be smaller in magnitude, bringing them into closer agreement with the trends in modern reanalyses and climate models. While the methodology presented here is statistical in nature, it produces quantitatively similar results to a more sophisticated mass budget correction method.
Hydroacoustic Measurements of the 2014 Eruption at Ahyi Volcano, 20.4°N Mariana Arc
Authors: Metz D. , Grevemeyer I.
Published: October 2018

Ahyi is a fully submerged arc volcano in the Northern Mariana Islands, northwestern Pacific Ocean. In April and May 2014, the volcano erupted over a period of 15 days. Results from direction‐of‐arrival calculations show that underwater sound phases associated with the episode were recorded as far as Wake Island, where a hydrophone triplet array is operated as part of the International Monitoring System. After a 3.5‐hr‐long sequence of hydroacoustic precursory events, explosive volcanic activity occurred in two distinct, several‐days‐long bursts, accompanied by a notable decrease in low‐frequency arrivals that may indicate a shift in signal source parameters. Acoustic resolution of the hydrophone data supersedes broadband networks by almost 1 order of magnitude, successfully identifying seismic events at Ahyi as low as 2.5 mb. Total radiated acoustic energy of the eruption is estimated at 6.4 1017 J, which suggests that submarine volcanic activity contributed significantly to the ocean soundscape.
On the Relationship Between Fault Permeability Increases, Induced Stress Perturbation, and the Growth of Aseismic Slip During Fluid Injection
Authors: Cappa Frédéric , Guglielmi Yves , Nussbaum Christophe , Birkholzer Jens
Published: October 2018

Fluid injections into the deep subsurface can, at times, generate earthquakes, but often, they only produce aseismic deformations. Here we analyze the influence of fault hydromechanical properties on the growth of injection‐induced aseismic slip. Using hydromechanical modeling, we show how permeability enhancement in addition to the background stress and frictional weakening has an important effect on the pressure diffusion and slip growth during injection. We find that the more pronounced the fault permeability enhancement, the stronger is the growth of the aseismic slip zone. The effect of enhanced permeability is more pronounced when the fault is initially close to failure. Our results show that aseismic slip grows beyond the pressurized zone when the fault permeability increases, while slip remains behind the pressurized zone when permeability does not vary from its initial preslip value. Thus, fault permeability increases should be considered as complementary mechanism to current models of fluid‐induced aseismic slip.
Crustal Heating and Lithospheric Alteration and Erosion Associated With Asthenospheric Upwelling Beneath Southern New England (USA)
Authors: Menke William , Lamoureux Juliette , Abbott Dallas , Hopper Emily , Hutson Dionne , Marrero Alyssa
Published: October 2018

The Northern Appalachian Anomaly (NAA), a region of exceptionally low seismic velocities in the asthenosphere beneath southern New England and easternmost New York State, has been interpreted as a site of mantle upwelling. We synthesize a combination of new and previously published data that indicates the following: (1) The upwelling has eroded or delaminated the lithosphere in a localized region centered in southern Vermont that we call the “Green Mountains Anomaly.” Forty‐second period Rayleigh wave phase velocities, which have peak sensitivity at lithospheric depths, are slow in this region, and S wave receiver functions are dominated by shallow (60‐km depth) mantle structures indicating reduced velocities. Thermal springs and sites with anomalously high concentrations of mantle‐derived helium‐3 are concentrated at the borders of the Green Mountains anomaly, perhaps due to stress concentrations produced by geologically recent, uncompensated delamination of the lower lithosphere. (2) S wave receiver functions indicate intense (>10%), shallow (60‐km depth) short wavelength structures along the southern and western edges of the NAA, indicating that the lithosphere there is being intensely altered, possibly by a combination of shearing and introduction of volatiles. And (3) Notwithstanding the localized thinning and alteration, the NAA lithosphere as a whole does not appear to have experienced pervasive heating, for the compressional wave quality factor of QP = 870 inferred from the decay rate of Po waves is very significantly above the QP ≈ 60 value previously reported for the NAA asthenosphere.
Limitations of the Resolvability of Finite‐Fault Models Using Static Land‐Based Geodesy and Open‐Ocean Tsunami Waveforms
Authors: Williamson Amy L. , Newman Andrew V.
Published: October 2018

Finite‐fault inversions are a common technique, employed following large earthquakes, used to understand the nature of slip along a fault. Using multiple data sets, including static offsets from geodetic instruments and tsunami wave heights from open‐ocean gauges, a richer perspective on the expected slip distribution than using a singular tool is created. However, the model resolution obtained from open‐ocean tsunami data and techniques used to subsample that data have not been widely evaluated. Static geodetic data can provide near‐complete model resolution of the subduction megathrust near the trench, if data are local. However, model resolution falls off precipitously as distance between instrument and fault increases when geodetic data are limited to more distal on‐land sites. Tsunami data derived from open‐ocean waveforms are less dependent on station to fault distance, but offshore model resolution is lost due to necessary data processing, such as windowing, often necessary to avoid coastal reflections. This primarily affects the resolution in the downdip direction, which often arrives at open‐ocean stations later in the waveform. Spatial detail is also limited by the minimum subfault size that will satisfy the longwave approximation, which is dependent on the water depth. For most cases, this subfault limit is approximately 20 by 20 km. In many environments, the sparsity of offshore geodetic instruments, and the large distances between estimated slip and coastal geodetic gauges, makes the inclusion of open‐ocean data, if available, highly advantageous. Still it is possible even with the pairing of on‐land and offshore data sets for poorly resolved zones to exist. In these cases further resolution can be recovered through the incorporation of additional data sets such as strong‐motion data and seismic waveforms through a seismic‐geodetic inversion.
An Alongshore Momentum Budget Over a Fringing Tropical Fore‐Reef
Authors: Arzeno Isabella B. , Collignon Audric , Merrifield Mark , Giddings Sarah N. , Pawlak Geno
Published: October 2018

Existing momentum budgets over coral reefs have predominantly focused on cross‐reef dynamics, lacking analysis of alongshore processes. To complement existing cross‐reef research and enhance our understanding of forcing variability at the semidiurnal period, this study examines the σ–coordinate, depth‐averaged alongshore momentum budget over a fore‐reef as a function of tidal phase. The observations were gathered over a 3‐week timespan, between the 12‐ and 20‐m isobaths of a Hawaiian fringing reef system, focusing on two moorings on the 12‐m isobath, where median drag coefficients estimated from log fits are CD=0.0080[−0.002,+0.004] and CD=0.0023[−0.0006,+0.0009]. Analysis at one location shows that the unsteadiness, barotropic pressure gradient, and bottom drag are equally important, and their combination is sufficient to close the momentum budget. However, bottom drag is less important at the second mooring; the difference between unsteadiness and pressure gradient suggests that advective acceleration plays a significant role.
Estimation of Specific Yield and its Variability by Electrical Resistivity Tomography
Authors: Dietrich Sebastian , Carrera Jesús , Weinzettel Pablo , Sierra Leonardo
Published: October 2018

Specific yield (Sy) is defined as the average volume of water that can be drained, per unit surface of aquifer per unit drop of head. This parameter is of critical relevance for groundwater resources assessment, but its estimation suffers from numerous difficulties, including spatial variability, hysteresis, dependence on depth to water table, or delayed drainage. As a result, no widely accepted method is available for its estimation. Here we show that most of these difficulties can be overcome by using time‐lapse electrical resistivity tomography (ERT) to map water content variations in response to phreatic level fluctuations. We applied the method to a synthetic example and to a real site in Argentina. Results demonstrate that the approach is robust and provides a picture of how, how much and where water is being released from the soil when aquifer heads drop, which is the ultimate goal of Sy concept. ERT produced some oscillations in estimated water contents, which we attribute to inversion artifacts. Still, the error analysis and the synthetic example suggest that the impact of spurious oscillations tends to cancel out during estimation of Sy, which supports the robustness of the method. Estimated Sy is sensitive to the petrophysical law. If the slope of this law is inadequate, calculated values of Sy may be biased, but their variability patterns are well captured by the method. What is clear is that Sy is a spatially and temporally variable parameter, whose estimation is difficult. ERT represents a possible avenue to evaluate Sy and its variability.
Tape nanolithography: a rapid and simple method for fabricating flexible, wearable nanophotonic devices
Authors: Wang Qiugu , Han Weikun , Wang Yifei , Lu Meng , Dong Liang
Published: October 2018

This paper describes a tape nanolithography method for the rapid and economical manufacturing of flexible, wearable nanophotonic devices. This method involves the soft lithography of a donor substrate with air-void nanopatterns, subsequent deposition of materials onto the substrate surface, followed by direct taping and peeling of the deposited materials by an adhesive tape. Without using any sophisticated techniques, the nanopatterns, which are preformed on the surface of the donor substrate, automatically emerge in the deposited materials. The nanopatterns can then be transferred to the tape surface. By leveraging the works of adhesion at the interfaces of the donor substrate-deposited material-tape assembly, this method not only demonstrates sub-hundred-nanometer resolution in the transferred nanopatterns on an area of multiple square inches but also exhibits high versatility and flexibility for configuring the shapes, dimensions, and material compositions of tape-supported nanopatterns to tune their optical properties. After the tape transfer, the materials that remain at the bottom of the air-void nanopatterns on the donor substrate exhibit shapes complementary to the transferred nanopatterns on the tape surface but maintain the same composition, thus also acting as functional nanophotonic structures. Using tape nanolithography, we demonstrate several tape-supported plasmonic, dielectric, and metallo-dielectric nanostructures, as well as several devices such as refractive index sensors, conformable plasmonic surfaces, and Fabry-Perot cavity resonators. Further, we demonstrate tape nanolithography-assisted manufacturing of a standalone plasmonic nanohole film and its transfer to unconventional substrates such as a cleaved facet and the curved side of an optical fiber.
Electrophysiological evidence for abnormal glutamate-GABA association following psychosis onset
Authors: Koshiyama Daisuke , Kirihara Kenji , Tada Mariko , Nagai Tatsuya , Fujioka Mao , Ichikawa Eriko , Ohta Kazusa , Tani Motoko , Tsuchiya Maiko , Kanehara Akiko , Morita Kentaro , Sawada Kingo , Matsuoka Jun , Satomura Yoshihiro , Koike Shinsuke , Suga Motomu , Araki Tsuyoshi , Kasai Kiyoto
Published: October 2018

Previous studies have shown glutamatergic dysfunction and γ-aminobutyric acid (GABA)-ergic dysfunction in schizophrenia. Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR) dysfunction and GABA-ergic dysfunction interact with each other and lead to alterations in excitatory/inhibitory balance. The NMDAR and GABAergic-interneuron functions may be indexed by mismatch negativity (MMN) and auditory steady-state gamma-band response (ASSR), respectively. However, no previous studies have tested the hypothesis of an abnormal association between MMN and gamma-band ASSR in the same patients to identify the in vivo evidence of NMDAR-GABA association during the early stages of psychosis. Participants were individuals with recent-onset schizophrenia (ROSZ; N = 21), ultra-high risk (UHR; N = 27), and healthy controls (HCs; N = 24). The MMN amplitude was significantly impaired in ROSZ (p = 0.001, d = 1.20) and UHR (p = 0.003, d = 1.01) compared with HCs. The intertrial phase coherence (ITC) index of gamma-band ASSR was significantly reduced in ROSZ compared with HCs (p < 0.001, d = –1.27) and UHR (p = 0.032, d = –0.75). The event-related spectral perturbation (ERSP) index of gamma-band ASSR was significantly smaller in ROSZ compared with HCs (p < 0.001, d = −1.21). The MMN amplitude was significantly correlated with the ITC in ROSZ (r = −0.69, p < 0.001). These findings provide the first in vivo evidence that an abnormal association of the electrophysiological indices of NMDAR and GABA dysfunctions may be present in recent-onset schizophrenia.
Hub-organized parallel circuits of central circadian pacemaker neurons for visual photoentrainment in Drosophila
Authors: Li Meng-Tong , Cao Li-Hui , Xiao Na , Tang Min , Deng Bowen , Yang Tian , Yoshii Taishi , Luo Dong-Gen
Published: October 2018

Circadian rhythms are orchestrated by a master clock that emerges from a network of circadian pacemaker neurons. The master clock is synchronized to external light/dark cycles through photoentrainment, but the circuit mechanisms underlying visual photoentrainment remain largely unknown. Here, we report that Drosophila has eye-mediated photoentrainment via a parallel pacemaker neuron organization. Patch-clamp recordings of central circadian pacemaker neurons reveal that light excites most of them independently of one another. We also show that light-responding pacemaker neurons send their dendrites to a neuropil called accessary medulla (aMe), where they make monosynaptic connections with Hofbauer–Buchner eyelet photoreceptors and interneurons that transmit compound-eye signals. Laser ablation of aMe and eye removal both abolish light responses of circadian pacemaker neurons, revealing aMe as a hub to channel eye inputs to central circadian clock. Taken together, we demonstrate that the central clock receives eye inputs via hub-organized parallel circuits in Drosophila.
Harnessing copper-palladium alloy tetrapod nanoparticle-induced pro-survival autophagy for optimized photothermal therapy of drug-resistant cancer
Authors: Zhang Yunjiao , Sha Rui , Zhang Lan , Zhang Wenbin , Jin Peipei , Xu Weiguo , Ding Jianxun , Lin Jun , Qian Jing , Yao Guangyu , Zhang Rui , Luo Fanchen , Zeng Jie , Cao Jie , Wen Long-ping
Published: October 2018

Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner. Inhibition of autophagy with 3-methyl adenine or chloroquine has a remarkable synergistic effect on TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR) and patient-derived breast cancer models, achieving a level of efficacy unattainable with TNP-2, the identically-shaped CuPd nanoparticles that have a higher photothermal conversion efficiency but no autophagy-inducing activity. Our results provide a proof-of-concept for a chemo-PTT strategy, which utilizes autophagy inhibitors instead of traditional chemotherapeutic agents and is particularly useful for eradicating drug-resistant cancer.
Myogenin promotes myocyte fusion to balance fibre number and size
Authors: Ganassi Massimo , Badodi Sara , Ortuste Quiroga Huascar Pedro , Zammit Peter S. , Hinits Yaniv , Hughes Simon M.
Published: October 2018

Each skeletal muscle acquires its unique size before birth, when terminally differentiating myocytes fuse to form a defined number of multinucleated myofibres. Although mice in which the transcription factor Myogenin is mutated lack most myogenesis and die perinatally, a specific cell biological role for Myogenin has remained elusive. Here we report that loss of function of zebrafish myog prevents formation of almost all multinucleated muscle fibres. A second, Myogenin-independent, fusion pathway in the deep myotome requires Hedgehog signalling. Lack of Myogenin does not prevent terminal differentiation; the smaller myotome has a normal number of myocytes forming more mononuclear, thin, albeit functional, fast muscle fibres. Mechanistically, Myogenin binds to the myomaker promoter and is required for expression of myomaker and other genes essential for myocyte fusion. Adult myog mutants display reduced muscle mass, decreased fibre size and nucleation. Adult-derived myog mutant myocytes show persistent defective fusion ex vivo. Myogenin is therefore essential for muscle homeostasis, regulating myocyte fusion to determine both muscle fibre number and size.
Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels
Authors: Tin Adrienne , Li Yong , Brody Jennifer A. , Nutile Teresa , Chu Audrey Y. , Huffman Jennifer E. , Yang Qiong , Chen Ming-Huei , Robinson-Cohen Cassianne , Macé Aurélien , Liu Jun , Demirkan Ayşe , Sorice Rossella , Sedaghat Sanaz , Swen Melody , Yu Bing , Ghasemi Sahar , Teumer Alexanda , Vollenweider Peter , Ciullo Marina , Li Meng , Uitterlinden André G. , Kraaij Robert , Amin Najaf , van Rooij Jeroen , Kutalik Zoltán , Dehghan Abbas , McKnight Barbara , van Duijn Cornelia M. , Morrison Alanna , Psaty Bruce M. , Boerwinkle Eric , Fox Caroline S. , Woodward Owen M. , Köttgen Anna
Published: October 2018

Elevated serum urate levels can cause gout, an excruciating disease with suboptimal treatment. Previous GWAS identified common variants with modest effects on serum urate. Here we report large-scale whole-exome sequencing association studies of serum urate and kidney function among ≤19,517 European ancestry and African-American individuals. We identify aggregate associations of low-frequency damaging variants in the urate transportersSLC22A12(URAT1;p = 1.3 × 10−56) andSLC2A9(p = 4.5 × 10−7). Gout risk in rareSLC22A12variant carriers is halved (OR = 0.5,p = 4.9 × 10−3). Selected rare variants inSLC22A12are validated in transport studies, confirming three as loss-of-function (R325W, R405C, and T467M) and illustrating the therapeutic potential of the new URAT1-blocker lesinurad. InSLC2A9, mapping of rare variants of large effects onto the predicted protein structure reveals new residues that may affect urate binding. These findings provide new insights into the genetic architecture of serum urate, and highlight molecular targets inSLC22A12andSLC2A9for lowering serum urate and preventing gout.
Local generation of hydrogen for enhanced photothermal therapy
Authors: Zhao Penghe , Jin Zhaokui , Chen Qian , Yang Tian , Chen Danyang , Meng Jin , Lu Xifeng , Gu Zhen , He Qianjun
Published: October 2018

By delivering the concept of clean hydrogen energy and green catalysis to the biomedical field, engineering of hydrogen-generating nanomaterials for treatment of major diseases holds great promise. Leveraging virtue of versatile abilities of Pd hydride nanomaterials in high/stable hydrogen storage, self-catalytic hydrogenation, near-infrared (NIR) light absorption and photothermal conversion, here we utilize the cubic PdH0.2 nanocrystals for tumour-targeted and photoacoustic imaging (PAI)-guided hydrogenothermal therapy of cancer. The synthesized PdH0.2 nanocrystals have exhibited high intratumoural accumulation capability, clear NIR-controlled hydrogen release behaviours, NIR-enhanced self-catalysis bio-reductivity, high NIR-photothermal effect and PAI performance. With these unique properties of PdH0.2 nanocrystals, synergetic hydrogenothermal therapy with limited systematic toxicity has been achieved by tumour-targeted delivery and PAI-guided NIR-controlled release of bio-reductive hydrogen as well as generation of heat. This hydrogenothermal approach has presented a cancer-selective strategy for synergistic cancer treatment.
Probing aggrephagy using chemically-induced protein aggregates
Authors: Janssen Anne F. J. , Katrukha Eugene A. , van Straaten Wendy , Verlhac Pauline , Reggiori Fulvio , Kapitein Lukas C.
Published: October 2018

Selective types of autophagy mediate the clearance of specific cellular components and are essential to maintain cellular homeostasis. However, tools to directly induce and monitor such pathways are limited. Here we introduce the PIM (particles induced by multimerization) assay as a tool for the study of aggrephagy, the autophagic clearance of aggregates. The assay uses an inducible multimerization module to assemble protein clusters, which upon induction recruit ubiquitin, p62, and LC3 before being delivered to lysosomes. Moreover, use of a dual fluorescent tag allows for the direct observation of cluster delivery to the lysosome. Using flow cytometry and fluorescence microscopy, we show that delivery to the lysosome is partially dependent on p62 and ATG7. This assay will help in elucidating the spatiotemporal dynamics and control mechanisms underlying aggregate clearance by the autophagy–lysosomal system.
Molecular determinants of post-mastectomy breast cancer recurrence
Authors: Keene Kimberly S. , King Tari , Hwang E. Shelley , Peng Bo , McGuire Kandace P. , Tapia Coya , Zhang Hong , Bae Sejong , Nakhlis Faina , Klauber-Demore Nancy , Meszoely Ingrid , Sabel Michael S. , Willey Shawna C. , Eterovic Agda Karina , Hudis Cliff , Wolff Antonio C. , De Los Santos Jennifer , Thompson Alastair , Mills Gordon B. , Meric-Bernstam Funda
Published: October 2018

Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1–3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1–3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This included 32 LRR, 34 DM, and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM, or controls. DNA analysis on 57 primary tumors (17 LRR, 15 DM, and 25 controls) identified significantly more NF1 mutations and mitogen-activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p < 0.0001 and p = 0.0070, respectively). Three patients had matched primary vs. LRR samples, one patient had a gain of a NF1 mutation in the LRR. There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression. The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) vs. controls (14%, p = 0.0045). In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype. Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence.
Benefits of Early Treatment for Patients with Hepatic Myelopathy Secondary to TIPS: A Retrospective Study in Northern China
Authors: Zhao Hongwei , Yue Zhendong , Wang Lei , Fan Zhenhua , He Fuliang , Dong Xiaoqun , Liu Fuquan
Published: October 2018

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective therapy for reducing portal pressure. Hepatic myelopathy (HM), a rare complication of chronic liver diseases, remains obscure in terms of treatment and prognosis. We aimed to determine an optimal treat strategy for patients with HM after TIPS. Twenty-nine patients who developed HM after TIPS were stratified by time-lapse from onset to treatment: group A (n = 16), <6 months; group B (n = 13), ≥6 months. Therapeutic measures included shunt-limiting and medical treatments. Overall survival, lower-limb muscle strength, Fugl-Meyer score, Barthel index, and serum ammonia were recorded. Median survival time in group A or B was 30 months or 16.5 months, respectively (log rank p = 0.0172). All patients in group A obtained improvement in grading of muscle strength (p < 0.0001), Fugl-Meyer score (p = 0.0021), and Barthel index (p = 0.0003), particularly male patients and those subjected to shunt-limiting. Serum ammonia levels were decreased significantly in both group A (p = 0.0007) and group B (p = 0.0007). Collectively, once HM is confirmed after TIPS, active intervention is imperative and urgent, especially within the first 6 months from onset of symptom. TIPS shunt-limiting is particularly beneficial for rehabilitation in patients with early-onset HM.
Effects of dietary protein restriction followed by realimentation on growth performance and liver transcriptome alterations of lamb
Authors: Cui K. , Wang B. , Ma T. , Si B. W. , Zhang N. F. , Tu Y. , Diao Q. Y.
Published: October 2018

The present study aimed to investigate the compensatory effect of early protein restriction followed by a realimentation on growth performance of lamb and to explore the transcriptomic changes in liver. Thirty-two lambs with an initial birth weight of 2.3 ± 0.20 kg that were weaned on day 15 were randomly divided into two groups. The lambs were fed a basal diet with normal protein level (NPL, protein level in the milk replacer and starter, 25 and 21%, respectively) or low protein level (LPL, protein level in the milk replacer and starter, 19 and 15%, respectively) from 15 to 60 d, after which all lambs consumed the same diet with a normal protein level from 61 to 90 d. Protein restriction led to a significant decrease in average daily gain (ADG), body weight and liver weight (P < 0.05). Transcriptome analysis showed that 302 or 12 differentially expressed genes (DEGs) were identified during the restriction or recovery periods, respectively (P < 0.05). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that DEGs enriched in nutrient metabolism and antioxidant capacity were down-regulated, while vessel development and immunity response-related genes up-regulated. The genes involved in metabolism of tyrosine were still down-regulated in the realimentation phase. Studies in this area indicated the accelerated growth effect of early protein restriction followed by a realimentation on growth performance of lambs and explored the transcriptomics change of liver which can help to develop feeding strategies to optimize the use of feedstuffs and in providing a new perspective for the study of early nutrition and epigenetics in later life.
Reduced graphene oxide triggered epithelial-mesenchymal transition in A549 cells
Authors: Liao Yanyan , Wang Weiyi , Huang Xiaomei , Sun Yongyan , Tian Shen , Cai Peng
Published: October 2018

Graphene and its derivatives have exhibited wide potential applications in electronics, structural engineering and medicine. However, over utilization and untreated discharge may cause its distribution into environmental as well as biological chain, which raised the concerns of potential health risk as a potential hazard. Accumulating evidence has demonstrated that graphene derivatives induce lung fibrosis in vivo, so overall goal of this study was to explore the molecular mechanisms underlying the pulmonary fibrotic responses of reduced graphene oxide (rGO), using in vitro assays. Epithelial-mesenchymal transition (EMT) has profound effect on development of pulmonary fibrosis. Herein, we evaluated the EMT effect of rGO samples on A549 cells. Firstly, rGO penetrated through the A549 cells membrane into the cytosol by endocytosis and located in late endosome and/or lysosomes observed via transmission electron microscopy (TEM), and were well tolerant by cells. Secondly, rGO promoted the cell migration and invasion capacities at lower doses (below 10 μg/ml), but significantly inhibited the capacities at 20 μg/ml. Moreover, rGO-induced EMT were evidenced by decreased expression of epithelial marker like E-cadherin, β-catenin, Smad4 and increased expression of mesenchymal markers like Vimentin, VEGF-B, TWIST1. Based on our findings, it is supposed that rGO can effectively induce EMT through altering epithelial–mesenchymal transition markers in A549 cells.
NLRP3 Inflammasome Modulates Post-Burn Lipolysis and Hepatic Fat Infiltration via Fatty Acid Synthase
Authors: Vinaik Roohi , Stanojcic Mile , Jeschke Marc G.
Published: October 2018

Burns result in generalized catabolism, lipolysis, and hyperinflammation. NLRP3 inflammasome, a mediator of hyperinflammation, is upregulated in burn patients’ adipose tissue within 7 days post-burn. However, its role during the acute phase is unknown. Here, wild-type (WT) and NLRP3 knockout (NLRP3−/−) mice were exposed to 25% TBSA scald burn. Flow cytometric analysis demonstrated greater liver macrophage infiltration in NLRP3−/− yet decreased protein expression of NLRP3 components, ER stress, and apoptosis. NLRP3−/− had increased circulating free fatty acids (FFA), fatty deposition and liver weight 1 hour post-burn. Alterations in adipose fatty acid synthase (Fasn) expression affects FFA levels post-burn; WT have an early peak in Fasn gene and protein expression that is lost in NLRP3−/−, resulting in increased lipolysis and hepatic fatty deposition. In summary, our findings reveal that NLRP3 inflammasome activation is a double-edged sword. While prolonged inflammation and long-term effects of macrophage activation are associated with poor outcomes, acute inflammation may be beneficial. These results highlight the important metabolic role that NLRP3 inflammasome plays in the acute phase, ultimately affecting survival post-burn.
Cytometric analysis of adipose tissue reveals increments of adipocyte progenitor cells after weight loss induced by bariatric surgery
Authors: García-Rubio Jesús , León Josefa , Redruello-Romero Anaïs , Pavón Esther , Cozar Antonio , Tamayo Francisco , Caba-Molina Mercedes , Salmerón Javier , Carazo Ángel
Published: October 2018

Obesity-related comorbidities are, in large part, originated from the dysfunction of adipose tissue. Most of them revert after the normalization of body mass. Adipose tissue is essentially occupied by adipocytes. However, different populations of immunological cells and adipocyte precursor cells (AdPCs) are the main cellular components of tissue. During obesity, body fat depots acquire a low-level chronic inflammation and adipocytes increase in number and volume. Conversely, weight loss improves the inflammatory phenotype of adipose tissue immune cells and reduces the volume of adipocytes. Nevertheless, very little is known about the evolution of the human AdPCs reservoir. We have developed a flow cytometry-based methodology to simultaneously quantify the main cell populations of adipose tissue. Starting from this technical approach, we have studied human adipose tissue samples (visceral and subcutaneous) obtained at two different physiological situations: at morbid obesity and after bariatric surgery-induced weight loss. We report a considerable increase of the AdPCs reservoir after losing weight and several changes in the immune cells populations of adipose tissue (mast cells increase, neutrophils decrease and macrophages switch phenotype). No changes were observed for T-lymphocytes, which are discussed in the context of recent findings.
Improving face identity perception in age-related macular degeneration via caricaturing
Authors: Lane Jo , Rohan Emilie M. F. , Sabeti Faran , Essex Rohan W. , Maddess Ted , Barnes Nick , He Xuming , Robbins Rachel A. , Gradden Tamara , McKone Elinor
Published: October 2018

Patients with age-related macular degeneration (AMD) have difficulty recognising people’s faces. We tested whether this could be improved using caricaturing: an image enhancement procedure derived from cortical coding in a perceptual ‘face-space’. Caricaturing exaggerates the distinctive ways in which an individual’s face shape differs from the average. We tested 19 AMD-affected eyes (from 12 patients; ages 66–93 years) monocularly, selected to cover the full range of vision loss. Patients rated how different in identity people’s faces appeared when compared in pairs (e.g., two young men, both Caucasian), at four caricature strengths (0, 20, 40, 60% exaggeration). This task gives data reliable enough to analyse statistically at the individual-eye level. All 9 eyes with mild vision loss (acuity ≥ 6/18) showed significant improvement in identity discrimination (higher dissimilarity ratings) with caricaturing. The size of improvement matched that in normal-vision young adults. The caricature benefit became less stable as visual acuity further decreased, but caricaturing was still effective in half the eyes with moderate and severe vision loss (significant improvement in 5 of 10 eyes; at acuities from 6/24 to poorer than <6/360). We conclude caricaturing has the potential to help many AMD patients recognise faces.
Microsphere-mediated optical contrast tuning for designing imaging systems with adjustable resolution gain
Authors: Migliozzi Daniel , Gijs Martin A. M. , Huszka Gergely
Published: October 2018

Upon illumination, a dielectric microsphere (μS) can generate a photonic nanojet (PNJ), which plays a role in the super-resolution imaging of a sample placed in the μS’s immediate proximity. Recent microscopy implementations pioneered this concept but, despite the experimental characterization and theoretical modeling of the PNJ, the key physical factors that enable optimization of such imaging systems are still debated. Here, we systematically analyzed the parameters that govern the resolution increase in the case of large-diameter (>20 µm) μS-assisted incoherent microscopy by studying both the illumination and the detection light paths. We determined the enhanced-resolution zone created by the μS, in which the detection system has a net resolution gain that we calculated theoretically and subsequently confirmed experimentally. Our results quantitatively describe the resolution enhancement mediated by the optical contrast between the μS and its surrounding medium, and provide concrete means for designing μS-enhanced imaging systems for several application requirements.
Ag surface segregation in nanoporous Au catalysts during CO oxidation
Authors: Pia Giorgio , Sogne Elisa , Falqui Andrea , Delogu Francesco
Published: October 2018

The present study focuses on the modification of surface compositional profiles induced in nanoporous (NP) Au catalysts by the catalytic oxidation of carbon monoxide to carbon dioxide in the presence of oxygen. The phenomenon has deep implications concerning the catalytic behavior of NP Au foams in particular, and more in general for the design of more efficient catalysts. Aimed at gaining deeper insight into the mechanisms governing surface segregation, we exposed NP Au foams containing residual Ag to a mixture of gaseous carbon monoxide and oxygen at different temperature. Structural and surface composition analyses pointed out the concomitant occurrence of both NP Au coarsening and Ag surface segregation processes. Experimental findings suggest for Ag surface segregation a two-stage kinetics. During the initial, rapid coarsening of the NP Au structure, Ag surface segregation is mediated by surface rearrangements, which allow the Ag atoms to reach the surface at anomalously fast rate. As coarsening decelerates, the slower diffusion of buried Ag atoms towards the surface predominates, due to favorable chemical interactions with adsorbed oxygen. This novel mechanism’s understanding can benefit strategic areas of science and technology.
Antiretroviral resistance, genotypic characterization and origin of Human Immunodeficiency Virus among the infected wives of Intravenous drug users in Manipur
Authors: Sharma Adhikarimayum Lakhikumar , Singh Thiyam Ramsing , Singh Lisam Shanjukumar
Published: October 2018

Increasing incidence of drug resistance is ascertained to be the main obstacles in limiting the virus among the human immunodeficiency virus (HIV) infected individuals. This study investigates the drug resistance mutations (DRMs), genetic variants and origin of transmitted drug resistance of HIV-1 among the HIV-1 infected wives of intravenous drug users (IDUs) in Manipur. 44 HIV pol gene sequences were generated from 56 blood samples by viral gene amplification and sequencing. Sequences were then analysed for drug resistance, genetic variants and origin. The result revealed that among the treatment naive cases, 35.7% had Transmitted Drug Resistance Mutations (TDRMs) while among treatment experienced cases, 50% had Acquired Drug Resistant Mutations (ADRMs). These TDRMs and ADRMs conferred resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and/or protease inhibitors (PIs). Majority of the isolated HIV-1 sequences (77.3%) were subtype C while 9.1% was discordant subtype, 6.8% was subtype B, 4.5% was CRF_01AE and 2.3% was URF_BC. TDRM strains were found to be introduced from Myanmar, Vietnam and mainland India. This study also reveals the appearance of CRF_01AE for the first time in Manipur. The finding of this study indicates high prevalence of drug resistant mutations and complex molecular epidemiology in Manipur.
CH3NH3PbX3 (X = I, Br) encapsulated in silicon carbide/carbon nanotube as advanced diodes
Authors: Zhang Lishu , Dai Xinyue , Li Tao , Li Jie , Li Hui
Published: October 2018

We employ first-principles density functional theory (DFT) calculations to study CH3NH3PbX3 (X = I, Br) and its encapsulation into the silicon carbide nanotube and carbon nanotube (CNT). Our results indicate that these devices show diode behaviors which act on negative bias voltage but do not work under positive voltage. When they are encapsulated into SiC nanotube and CNT, their electronic properties would be changed, especially, electric currents mainly exist at positive bias region. Corresponding transmission spectra and density of states are provided to interpret the transport mechanism of the CH3NH3PbX3 (X = I, Br) as a diode. These findings open a new door to microelectronics and integrated circuit components, providing theoretical foundation for innovation of the new generation of electronic materials.
Graphene, electrospun membranes and granular activated carbon for eliminating heavy metals, pesticides and bacteria in water and wastewater treatment processes
Authors: Rajapaksha P. Piumie , Power Aoife , Chandra Shaneel , Chapman James
Published: October 2018

The availability of safe water has a significant impact on all parts of society, its growth and sustainability, both politically and socioeconomically.