bluuebunny/crossref_metadata_2025 huggingface dataset:
Tobacco Use in Adults With Mental Illness: An Overview of One State-Wide Tobacco Cessation Program
Authors: Sarfraz Noeen , Fils-Aime Yvon , Brand Michael , Vesely Sara , Beebe Laura
Published: July 2018

Even though one of the public health's top achievements of the 20th century involves tobacco cessation, a disproportionate burden of tobacco-related comorbidity still affects those with mental illness (Centers for Disease Control and Prevention, 2017; Cook et al., 2014). There is evidence suggesting that psychiatric disorders are associated with an increased prevalence in cigarette smoking (Tsoi, Porwa, & Webster, 2013). One explanation for this is the potentiating effect of nicotine on dopamine receptors (Mao, Gallagher, & McGehee, 2011). Other explanations include poverty, educational advancement and industry bias in tobacco marketing (MMWR Vital Signs: Current Cigarette, 2016; CDC Morbidity and Mortality, 2013). We know that adults with mental illness smoke at rates twice that of the general population, and are nicotine-dependent at rates up to three times higher than the general population (Cook et al., 2014; Grant, Hasin, Chou, Stinson, & Dawson, 2004). Adults with mental illness comprise about 19% of the population, but smoke approximately one-third of all the cigarettes smoked (MMWR Vital Signs: Current Cigarette, 2016). In the United States, the national tobacco use prevalence is estimated at 19%; however, prevalence among those with bipolar disorder is 51%–70% and 36%–80% among those with major depressive disorder (Grant et al., 2004; King, Dube, & Tynan, 2012; Lasser et al., 2000). Despite these high rates, recent studies suggest that smokers with mental illness are highly motivated to quit (Cook et al., 2014). However, it remains rare for mental and behavioural health professionals to offer tobacco cessation pharmacotherapy and counselling to clients with psychiatric disorders.
Contemporary animal advocacy in Italy
Authors: Bertuzzi Niccolò
Published: July 2018

In spite of the great tradition in social movement studies, Italy completely lacks any contribution regarding animal advocacy from the point of view of political sociology. This is despite the fact that, as in the rest of Western societies, interest in the wellbeing, rights and status of non-human animals is growing. This can be seen both among the general population and in the very varied organised forms of welfare and activism. In this article, we will investigate this internal differentiation, starting from an initial stratification in welfare, protectionism and anti-speciesism, and focusing in particular on the following two aspects: ethical values; and political ‘careers’ and multi-membership affiliations. The investigation was accomplished by means of 20 semi-structured interviews and an online questionnaire answered by 704 volunteers and activists. The tripartition hypothesised was confirmed, although with a few exceptions: more progressive values emerged among anti-speciesists, and conservative positions among protectionists and welfarists, but the overall spectrum is characterised by utilitarian perspectives. Similarly, previous experience in the specific field of animal advocacy is typical of the protectionist area, while anti-speciesists also come from other opposition movements.
Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation
Authors: He Jintian , Niu Yu , Wang Fei , Wang Chao , Cui Tao , Bai Kaiwen , Zhang Jingfei , Zhong Xiang , Zhang Lili , Wang Tian
Published: July 2018

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1βand IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT andNfe2l2/AREpathways in the liver.
Global and Local: Retail Transformation and the Department Store in Britain and Japan, 1900–1940
Authors: Fujioka Rika , Stobart Jon
Published: July 2018

Department stores are often seen as transformative of both retail and wider social practices. This article offers a comparative analysis of department stores in early twentieth-century Britain and Japan to assess the extent to which there were universal qualities defining the operation, practices, and experience of department stores and to explore the ways in which they might be seen as transforming retailing in the two countries. Despite similarities in their origin, organization, and service to customers, we highlight the greater diversity of British department stores and their incremental development. Japanese stores were a far more powerful force for change because they formed part of a concerted and conscious program of modernization.
Reassessing the Italian “Economic Miracle”: Law, Firms’ Governance, and Management, 1950–1973
Authors: Di Martino Paolo , Vasta Michelangelo
Published: July 2018

This article revisits and reassesses the evolution of Italian capitalism during the so called “economic miracle” (1950–1973). Using original sources, it analyzes how the average small, private firm, representing the vast majority of Italian businesses at the time, struggled to fully develop, grow, and modernize. The paper identifies the main source of the problem in a set of inefficient (or poorly-enforced) laws and regulations that allowed firms to remain competitive, and business owners to extract resources out of them, using a wide variety of borderline strategies. This article also claims that accountants (commercialisti) had a key role in implementing these strategies.
Laser-driven electron acceleration in hydrogen pair-ion plasma containing electron impurities
Authors: Kargarian A. , Hajisharifi K. , Mehdian H.
Published: July 2018

In this paper, the intense laser heating of hydrogen pair-ion plasma with and without electron impurities through investigation of related nonlinear phenomena has been studied in detail, using a developed relativistic particle-in-cell simulation code. It is shown that the presence of electron impurities has an essential role in the behavior of nonlinear phenomena contributing to the laser absorption including phase mixing, wave breaking, and stimulated scatterings. The inclusion of electron into an initial pure hydrogen plasma not only causes the occurrence of stimulated scattering considerably but also leads to the faster phase-mixing and wave breaking of the excited electrostatic modes in the system. These nonlinear phenomena increase the laser absorption rate in several orders of magnitude via inclusion of the electrons into a pure hydrogen pair-ion plasma. Moreover, results show that the electrons involved in enough low-density hydrogen pair-ion plasma can be accelerated to the MeV energy range.
Congenital superior caval vein aneurysm in a newborn with cystic lymphangioma: a rare case report
Authors: Attene Jessica , Casorelli Ernesto , Versacci Paolo
Published: July 2018

Dilatation of the superior caval vein is extremely rare, with few cases described among newborns. The association of aneurysm of the superior caval vein and lymphatic malformation is extremely uncommon. We report a case of a female infant with a prenatal diagnosis of superior caval vein aneurysm presenting at birth with a neck mass that was found to be a cystic lymphangioma.
The eye in CHD
Authors: Nasir-Ahmad Subha , Cordina Rachael , Liew Gerald , McCluskey Peter , Celermajer David
Published: July 2018

In recent years, there has been a rise in the number patients with CHD surviving into adulthood. Many have complications related to their CHD or its treatments, outside the heart, including ocular abnormalities. The objective of this review is to highlight the ocular abnormalities that occur in adults with CHD, either from their condition or related to the common drugs prescribed to manage it. In particular, we reviewed the effects of cyanosis, coarctation of the aorta, endocarditis, and the side effects of Sildenafil and Amiodarone. A change in the retinal vasculature is a common observation with cyanosis or coarctation of the aorta. Occlusion of the retinal vessels may also be observed in cyanotic patients, as well as those with infectious endocarditis. Sildenafil has established ocular side effects; here they are explored in the context of therapy for pulmonary hypertension. Similarly, Amiodarone has established ocular risks, which are summarised. The high prevalence of ocular consequences in adult CHD patients reinforces the need for knowledge of the risks involved and for frequent ophthalmological screening where appropriate.
Arthropod pest complex and associated damage in field-grown tomato in Senegal
Authors: Diatte Mamadou , Brévault Thierry , Sylla Serigne , Tendeng Etienne , Sall-Sy Dienaba , Diarra Karamoko
Published: July 2018

Biotic factors (including insect pests) constrain field-grown tomato production in Senegal. However, little information is available on the identity and life system of key pests. The objectives of this study were to: (i) update key pest records of field-grown tomato in the central vegetable-producing area along the northern coast of Senegal, known as the Niayes area; (ii) map their spatial and temporal incidence and (iii) understand insecticide use by growers to control the pests. A total of 98 tomato fields distributed in three zones along a north–south transect in the Niayes area were monitored over four crop cycles from 2012 to 2014. As expected, the tomato fruitworm Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) was the most destructive pest with an occurrence of 92% in sampled fields (90/98) and up to 38% damaged fruits in one field at the time of sampling. The proportion of damaged fruits did not differ among zones, but was significantly higher in the early dry season compared to the late dry season. The invasive tomato leafminer Tuta absoluta Meyrick (Lepidoptera: Gelechiidae) was detected in 53% of sampled fields (52/98), mainly in the south of the Niayes area in the late dry season. Because of their ability to adapt to unstable environment and insecticides, this insect pest assemblage is a new challenge that farmers have to deal with while decreasing their use of broad-spectrum insecticides.
Identifying the Recurrence Patterns of Nonvolcanic Tremors Using a 2‐D Hidden Markov Model With Extra Zeros
Authors: Wang Ting , Zhuang Jiancang , Buckby Jodie , Obara Kazushige , Tsuruoka Hiroshi
Published: July 2018

Nonvolcanic tremor activity has been observed in many places worldwide. In some regions, their activity was observed to accompany slow slip events. Before examining whether and how nonvolcanic tremor activity is related to slow slip, it is essential to understand quantitatively the spatiotemporal migration patterns of nonvolcanic tremors. We developed a 2‐D hidden Markov model to automatically analyze and forecast the spatiotemporal behavior of tremor activity in the regions Kii and Shikoku, southwest Japan. This new automated procedure classifies the tremor source regions into distinct segments in 2‐D space and infers a clear hierarchical structure of tremor activity, where each region consists of several subsystems and each subsystem contains several segments. The segments can be quantitatively categorized into three different types according to their occurrence patterns: episodic, weak concentration, and background, extending earlier knowledge gained from handpicked tremor swarms. The Kii region can be categorized into four different subsystems, with two often linked to each other. The Shikoku region can be divided into six subsystems, with two in central Shikoku linked to each other. Moreover, a significant increase in the proportion of tremor occurrence was detected in a segment in southwest Shikoku before the 2003 and 2010 long‐term slow slip events in the Bungo channel. This highlights the possible correlation between nonvolcanic tremor and slow slip events. The model can be used to analyze tremor data from other regions.
Satellite‐Observed Impacts of Wildfires on Regional Atmosphere Composition and the Shortwave Radiative Forcing: A Multiple Case Study
Authors: Fu Yuyun , Li Rui , Huang Jianguo , Bergeron Yves , Fu Yunfei , Wang Yu , Gao Zongting
Published: July 2018

Emissions of aerosols and trace gases from wildfires and their direct shortwave radiative forcing (DSRF) at the top of atmosphere were studied using satellite observations from Moderate‐Resolution Imaging Spectroradiometer, Atmospheric Infrared Sounder, Clouds and Earth Radiant Energy System on Aqua, and Ozone Monitoring Instrument on Aura. The dominant fuel types of the selected fire cases in the northeast of China (NEC), Siberia (Russia), and California (USA) are cropland, mixed forest, and needle‐leaf forest, respectively. For the cropland fire case in NEC, the fire radiative power‐based emission coefficients (Ce) of aerosol is 20.51 ± 2.55 g/MJ, half that of the forest fire cases in Siberia (40.01 ± 9.21 g/MJ) and California (45.23 ± 8.81 g/MJ), and the carbon monoxide (CO) Ce (23.94 ± 11.83 g/MJ) was about one third and half that of the forest fire cases in Siberia and California, respectively. However, the NOx (NO2 + NO) Ce (2.76 ± 0.25g MJ−1) of the cropland fire in NEC was nearly 3 times that of those forest fire cases. Ratios of NOx to aerosol, HCHO, and CO in the cropland case in NEC show much higher values than those in the forest fire cases. Despite the differences of the Ce and the composition ratios, the DSRF efficiency of smoke aerosol at the top of atmosphere showed similar values among those fire cases. Our results highlight the large variability of emission rate and relative chemical composition but similar DSRF efficiencies among wildfires, which would provide valuable information for understanding the impact of fire on air quality and climate.
Generation of High Mountain Precipitation and Temperature Data for a Quantitative Assessment of Flow Regime in the Upper Yarkant Basin in the Karakoram
Authors: Kan Baoyun , Su Fengge , Xu Baiqing , Xie Ying , Li Jiule , Zhang Hongbo
Published: July 2018

Improved daily precipitation and temperature data at 5 × 5‐km grids for 1960–2015 were developed for the Upper Yarkant basin (UYB) based on observations of precipitation gradients and temperature lapse rates. The developed climate data are then used to drive the VIC‐Glacier hydrological model to simulate the runoff process for the UYB. A large altitudinal dependence is observed in both precipitation and temperature, with three altitudinal patterns of precipitation gradient for the elevation bands of <2,000 m, 2,000–3,000 m, and >3,000 m, respectively, and a strong seasonal variation in temperature lapse rate ranging from 0.4 to 0.8 °C/100 m. Basin precipitation and temperature data are greatly improved in both amount and spatial variations after the orographic adjustments. Glacier melt runoff is the dominant water source of the UYB accounting for about 52% of annual total flows, followed by snowmelt (about 26%), and rainfall runoff (about 22%). About 60% of basin runoff originates from the high altitudes (>5,000 m), and about 32% and 8% of runoff originate from middle (4,000–5,000 m) and low (<4,000 m) altitudes, respectively. The variations in annual runoff in the UYB were mainly controlled by glacier melt runoff, middle and high altitudes, and temperature in warm seasons during 1965–2015. However, rainfall and snowmelt runoff, and low altitudes, were playing an increasingly important role in total flow variations of the UYB due to the increase of warm season temperatures in 1994–2015 and precipitation in the entire simulation period.
Determining the Wave Vector Direction of Equatorial Fast Magnetosonic Waves
Authors: Boardsen Scott A. , Hospodarsky George B. , Min Kyungguk , Averkamp Terrance F. , Bounds Scott R. , Kletzing Craig A. , Pfaff Robert F.
Published: July 2018

We perform polarization analysis of the equatorial fast magnetosonic waves electric field over a 20‐min interval of Van Allen Probes A waveform receiver burst mode data. The wave power peaks at harmonics of the proton cyclotron frequency indicating that the spacecraft is near or in the source region. The wave vector is inferred from the direction of the major axis of the electric field polarization ellipsoid and the sign of the phase between the longitudinal electric and compressional magnetic field components. We show that wave vector is preferentially in the azimuthal direction as opposed to the radial direction. From Poynting flux analysis one would infer that the wave vector is primarily in the radial direction. We show that the error in the Poynting flux is large ~90°. These results strongly imply that the wave growth occurs during azimuthal propagation in the source region for this event.
Chemical Diversity of Sands Within the Linear and Barchan Dunes of the Bagnold Dunes, Gale Crater, as Revealed by APXS Onboard Curiosity
Authors: O'Connell‐Cooper C. D. , Thompson L. M. , Spray J. G. , Berger J. A. , VanBommel S. J. , Gellert R. , Boyd N. I. , DeSouza E.
Published: July 2018

Alpha Particle X‐ray Spectrometer (APXS) results for Phase 2 of the Bagnold Dunes campaign, focusing on the linear dunes, complement those from Phase 1 (barchan dunes) and add to our understanding of active Martian dune systems. This work highlights both compositional similarities and differences across the dune field. The concentration of elements associated with mafic minerals in coarser grains and along active ripple crests, previously identified in the barchan dunes, highlights differences in Martian and terrestrial weathering, transport, and sorting processes. Concentration of a Cr‐Ti mineral phase within the linear sands is identified. The inactive ripple fields are geochemically similar to soil, while active ripple fields are similar to sands. Inferred dust content (S + Cl + Zn concentrations), derived from APXS analyses, provide geochemical confirmation of current and seasonal activity variations, within the barchan and linear dunes, as well as revealing a continuum between inactive soils and active sands.
The Composition of Plasma inside Geostationary Orbit Based on Van Allen Probes Observations
Authors: Yue Chao , Bortnik Jacob , Li Wen , Ma Qianli , Gkioulidou Matina , Reeves Geoffrey D. , Wang Chih‐Ping , Thorne Richard M. , Lui Anthony T. Y. , Gerrard Andrew J. , Spence Harlan E. , Mitchell Donald G.
Published: July 2018

The composition of the inner magnetosphere is of great importance for determining the plasma pressure and thus the currents and magnetic field configuration. In this study, we perform a statistical survey of equatorial plasma pressure distributions and investigate the relative contributions of ions and electron with different energies inside of geostationary orbit under two auroral electrojet levels based on over 60 months of observations from the Helium, Oxygen, Proton, and Electron and Radiation Belt Storm Probes Ion Composition Experiment mass spectrometers onboard Van Allen Probes. We find that the total and partial pressures of different species increase significantly at high auroral electrojet levels with hydrogen pressure being dominant in the plasmasphere. The pressures of the heavy ions and electrons increase outside the plasmapause and develop a strong dawn‐dusk asymmetry with ion pressures peaking at dusk and electron pressure peaking at dawn. In addition, ring current hydrogen with energies ranging from 50 keV up to several hundred keV is the dominant component of plasma pressure during both quiet (>90%) and active times (>60%), while oxygen with 10 < E < 50 keV and electrons with 0.1 < E < 40 keV become important during active times contributing more than 25% and 20% on the nightside, respectively, while the helium contribution is generally small. The results presented in this study provide a global picture of the equatorial plasma pressure distributions and the associated contributions from different species with different energy ranges, which advance our knowledge of wave generation and provide models with a systematic baseline of plasma composition.
Incorporating a Large‐Scale Constraint Into Radar Data Assimilation to Mitigate the Effects of Large‐Scale Bias on the Analysis and Forecast of a Squall Line Over the Yangtze‐Huaihe River Basin
Authors: Yue Xinjian , Shao Aimei , Fang Xue , Li Lanqian
Published: July 2018

When there is an obvious large‐scale bias between a regional simulation and its driving global analysis, the regional model will provide inaccurate background information for radar data assimilation, which may eventually yield location errors associated with predicted precipitation. A case study of a squall line over the Yangtze‐Huaihe river basin presents such a situation. In this regard, we propose an approach to incorporate a large‐scale constraint into radar data assimilation to mitigate the effects of large‐scale bias on analysis and forecast results, in which global analysis data are introduced into the regional model using the spectral nudging technique to improve the quality of the first guess and background error statistics in radar data assimilation. A series of experiments are conducted with the Weather Research and Forecasting model and its three‐dimensional variational system to investigate the effectiveness of the proposed approach to introduce a large‐scale constraint into radar data assimilation. The experimental results demonstrate that the introduction of global analysis data can effectively correct the large‐scale bias and significantly improve the forecast skill of large‐scale patterns and convection initiation. The background error covariance (BE) obtained with the large‐scale constraint plays an important role in improving the assimilation effect. The length scales of BE are reduced after the large‐scale bias is removed, which represents a partial solution to the overestimation of BE reported in previous studies. In addition, applying a larger nudging wave number to radar data assimilation domain is not appropriate because the use of a larger wave number can negatively impact the three‐dimensional variational analysis.
Wind Dynamics Over a Highly Heterogeneous Oasis Area: An Experimental and Numerical Study
Authors: Liu Rui , Liu Shaomin , Yang Xiaofan , Lu Hui , Pan Xiaoduo , Xu Ziwei , Ma Yanfei , Xu Tongren
Published: July 2018

Oases are unique heterogeneous landscapes that coexist within the Gobi desert in the arid and semiarid regions, which are vital for agricultural production and economic development. The heterogeneity of the land surface with vegetation will significantly influence the wind dynamics and airflow characteristics. The current study utilized an integrated approach, combining the computational fluid dynamics (CFD) method with the k‐ɛ turbulence model and high‐resolution ground‐measurement data to analyze the wind dynamics over an oasis. Specifically, (1) the Weather Research and Forecast model (WRF) data were used as boundary conditions to initiate the simulations; (2) the canopy leaf area density estimated from airborne laser scanning data was added as the source terms of the momentum and turbulence transport equations, which represented the highly heterogeneous vegetation structures in the oasis area. CFD‐simulated wind field results agreed well with the flux observation matrix data (17 tower measurements in a 5.5 km × 5.5 km experimental area). The spatial and temporal variations of wind fields affected by heterogeneous land surfaces were successfully captured. The CFD‐simulated wind fields also clearly showed the “wind shield effect” over highly heterogeneous land surfaces, wherein the existence of shorter and longer wind speed reduction areas at the windward and leeward sides of the shelterbelts contribute to protecting farmlands and orchards from wind erosion. In addition, the current approach of estimating aerodynamic roughness length (z0m) based on high‐resolution CFD‐simulated wind profiles was demonstrated to be a promising method of capturing wind dynamics over heterogeneous surfaces.
A TRMM Assessment of the Composition of the Generator Current That Supplies the Global Electric Circuit
Authors: Peterson Michael , Deierling Wiebke , Liu Chuntao , Mach Douglas , Kalb Christina
Published: July 2018

The Peterson et al. (2015, https://doi.org/10.1175/JTECH-D-14-00119.1) passive microwave electric field retrieval is applied to 15 years of Tropical Rainfall Measuring Mission (TRMM) satellite observations to estimate the amount of Wilson current supplied to the Global Electric Circuit from individual electrified cloud features (ECFs), which are identified as contiguous precipitating cloud regions that produce Wilson current. Current contributions from 37 million ECFs sampled by TRMM are used to examine the composition of the DC generator current. Thunderstorms are found to supply 61% of the total retrieved current, while electrified shower clouds provide the remaining 39%. ECFs over land contribute 38% of the total current, while the ocean contributions are divided between coastal oceanic regions (35%) and the open ocean (27%). The greatest share of the total TRMM‐retrieved current comes large mesoscale features (>2 × 103 km2 in area) and features that have peak 20‐km electric fields in excess of 1 kVm−1. This combination of extent and intensity leads to total currents greater than 10 A for a single ECF. The ranking of the tropical chimney regions by total current production is (1) the Americas (38%), (2) Asia (32%), and (3) Africa (15%). ECFs over the tropical Pacific Ocean contribute the remaining 15%. The Africa chimney is most prominent in total lightning activity but lags behind the others in total DC current due to a reduced frequency of electrified weather and weaker per‐storm electric fields and Wilson currents compared to the other chimneys.
Fully integrated wearable impedance cytometry platform on flexible circuit board with online smartphone readout
Authors: Furniturewalla Abbas , Chan Matthew , Sui Jianye , Ahuja Karan , Javanmard Mehdi
Published: July 2018

We present a wearable microfluidic impedance cytometer implemented on a flexible circuit wristband with on-line smartphone readout for portable biomarker counting and analysis. The platform contains a standard polydimethylsiloxane (PDMS) microfluidic channel integrated on a wristband, and the circuitry on the wristband is composed  of a custom analog lock-in amplification system, a microcontroller with an 8-bit analog-to-digital converter (ADC), and a Bluetooth module wirelessly paired with a smartphone. The lock-in amplification (LIA) system is implemented with a novel architecture which consists of the lock-in amplifier followed by a high-pass filter stage with DC offset subtraction, and a post-subtraction high gain stage enabling detection of particles as small as 2.8  μm using the 8-bit ADC. The Android smartphone application was used to initiate the system and for offline data-plotting and peak counting, and supports online data readout, analysis, and file management. The data is exportable to researchers and medical professionals for in-depth analysis and remote health monitoring. The system, including the microfluidic sensor, microcontroller, and Bluetooth module all fit on the wristband with a footprint of less than 80 cm2. We demonstrate the ability of the system to obtain generalized blood cell counts; however the system can be applied to a wide variety of biomarkers by interchanging the standard microfluidic channel with microfluidic channels designed for biomarker isolation.
Systems analysis of intracellular pH vulnerabilities for cancer therapy
Authors: Persi Erez , Duran-Frigola Miquel , Damaghi Mehdi , Roush William R. , Aloy Patrick , Cleveland John L. , Gillies Robert J. , Ruppin Eytan
Published: July 2018

A reverse pH gradient is a hallmark of cancer metabolism, manifested by extracellular acidosis and intracellular alkalization. While consequences of extracellular acidosis are known, the roles of intracellular alkalization are incompletely understood. By reconstructing and integrating enzymatic pH-dependent activity profiles into cell-specific genome-scale metabolic models, we develop a computational methodology that explores how intracellular pH (pHi) can modulate metabolism. We show that in silico, alkaline pHi maximizes cancer cell proliferation coupled to increased glycolysis and adaptation to hypoxia (i.e., the Warburg effect), whereas acidic pHi disables these adaptations and compromises tumor cell growth. We then systematically identify metabolic targets (GAPDHandGPI) with predicted amplified anti-cancer effects at acidic pHi, forming a novel therapeutic strategy. Experimental testing of this strategy in breast cancer cells reveals that it is particularly effective against aggressive phenotypes. Hence, this study suggests essential roles of pHi in cancer metabolism and provides a conceptual and computational framework for exploring pHi roles in other biomedical domains.
Optical imaging of metabolic dynamics in animals
Authors: Shi Lingyan , Zheng Chaogu , Shen Yihui , Chen Zhixing , Silveira Edilson S. , Zhang Luyuan , Wei Mian , Liu Chang , de Sena-Tomas Carmen , Targoff Kimara , Min Wei
Published: July 2018

Direct visualization of metabolic dynamics in living animals with high spatial and temporal resolution is essential to understanding many biological processes. Here we introduce a platform that combines deuterium oxide (D2O) probing with stimulated Raman scattering (DO-SRS) microscopy to image in situ metabolic activities. Enzymatic incorporation of D2O-derived deuterium into macromolecules generates carbon–deuterium (C–D) bonds, which track biosynthesis in tissues and can be imaged by SRS in situ. Within the broad vibrational spectra of C–D bonds, we discover lipid-, protein-, and DNA-specific Raman shifts and develop spectral unmixing methods to obtain C–D signals with macromolecular selectivity. DO-SRS microscopy enables us to probe de novo lipogenesis in animals, image protein biosynthesis without tissue bias, and simultaneously visualize lipid and protein metabolism and reveal their different dynamics. DO-SRS microscopy, being noninvasive, universally applicable, and cost-effective, can be adapted to a broad range of biological systems to study development, tissue homeostasis, aging, and tumor heterogeneity.
Distributed forward Brillouin sensor based on local light phase recovery
Authors: Chow Desmond M. , Yang Zhisheng , Soto Marcelo A. , Thévenaz Luc
Published: July 2018

The distributed fibre sensing technology based on backward stimulated Brillouin scattering (BSBS) is experiencing a rapid development. However, all reported implementations of distributed Brillouin fibre sensors until today are restricted to detecting physical parameters inside the fibre core. On the contrary, forward stimulated Brillouin scattering (FSBS), due to its resonating transverse acoustic waves, is being studied recently to facilitate innovative detections in the fibre surroundings, opening sensing domains that are impossible with BSBS. Nevertheless, due to the co-propagating behaviour of the pump and scattered lights, it is a challenge to position-resolve FSBS information along a fibre. Here we show a distributed FSBS analysis based on recovering the FSBS induced phase change of the propagating light waves. A spatial resolution of 15 m is achieved over a length of 730 m and the local acoustic impedances of water and ethanol in a 30 m-long uncoated fibre segment are measured, agreeing well with the standard values.
Highly-efficient extraction of entangled photons from quantum dots using a broadband optical antenna
Authors: Chen Yan , Zopf Michael , Keil Robert , Ding Fei , Schmidt Oliver G.
Published: July 2018

Many quantum photonic technologies require the efficient generation of entangled pairs of photons, but to date there have been few ways to produce them reliably. Sources based on parametric down conversion operate at very low efficiency per pulse due to the probabilistic generation process. Semiconductor quantum dots can emit single pairs of entangled photons deterministically but they fall short due to the extremely low-extraction efficiency. Strategies for extracting single photons from quantum dots, such as embedding them in narrowband optical cavities, are difficult to translate to entangled photons. Here, we build a broadband optical antenna with an extraction efficiency of 65% ± 4% and demonstrate a highly-efficient entangled-photon source by collecting strongly entangled photons (fidelity of 0.9) at a pair efficiency of 0.372 ± 0.002 per pulse. The high brightness achieved by our source represents a step forward in the development of optical quantum technologies.
GM-CSF driven myeloid cells in adipose tissue link weight gain and insulin resistance via formation of 2-aminoadipate
Authors: Plubell Deanna L. , Fenton Alexandra M. , Wilmarth Phillip A. , Bergstrom Paige , Zhao Yuqi , Minnier Jessica , Heinecke Jay W. , Yang Xia , Pamir Nathalie
Published: July 2018

In a GM-CSF driven myeloid cell deficient mouse model (Csf2−/−) that has preserved insulin sensitivity despite increased adiposity, we used unbiased three-dimensional integration of proteome profiles, metabolic profiles, and gene regulatory networks to understand adipose tissue proteome-wide changes and their metabolic implications. Multi-dimensional liquid chromatography mass spectrometry and extended multiplex mass labeling was used to analyze proteomes of epididymal adipose tissues isolated fromCsf2+/+andCsf2−/−mice that were fed low fat, high fat, or high fat plus cholesterol diets for 8 weeks. The metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, phospholipids, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet for both genotypes, while mice lacking Csf2 were protected from insulin resistance. Regardless of diet, 30 mostly mitochondrial, branch chain amino acids (BCAA), and lysine metabolism proteins were altered betweenCsf2−/−andCsf2+/+mice (FDR < 0.05). Lack of GM-CSF driven myeloid cells lead to reduced adipose tissue 2-oxoglutarate dehydrogenase complex (DHTKD1) levels and subsequent increase in plasma 2-aminoadipate (2-AA) levels, both of which are reported to correlate with insulin resistance. Tissue DHTKD1 levels were >4-fold upregulated and plasma 2-AA levels were >2 fold reduced inCsf2−/−mice (p < 0.05). GM-CSF driven myeloid cells link peripheral insulin sensitivity to adiposity via lysine metabolism involving DHTKD1/2-AA axis in a diet independent manner.
Poor oral health and risk of incident myocardial infarction: A prospective cohort study of Swedish adults, 1973–2012
Authors: Wilson Katherine , Liu Zhiwei , Huang Jiaqi , Roosaar Ann , Axéll Tony , Ye Weimin
Published: July 2018

Previous studies provide conflicting evidence as to whether there is an association between poor oral health and an increased risk of myocardial infarction. The aim of the study was to deepen knowledge of the association between oral health and myocardial infarction risk using a large (n = 20,133), prospective, and population-based cohort in Uppsala, Sweden. Oral health was determined during a clinical dental examination at entry into the cohort in 1973/74. Individuals were followed through linkage with the Swedish National Patient Register, Cause of Death Register and Emigration Register. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) for total, non-fatal and fatal myocardial infarction events. Increased risks of total, non-fatal and fatal myocardial infarction events among individuals with fewer reference teeth at examination, more dental plaque and a borderline significant increased risk among individuals with oral lesions were observed. Adjustment for multiple potential confounding factors did not change the results appreciably. However, the observed HRs generally decreased towards one when the analysis was confined to non-tobacco users only. The results from this study indicate that poor oral health is associated with a slightly increased risk of myocardial infarction; however, these results may be partly explained by residual confounding.
Influence of the sebaceous gland density on the stratum corneum lipidome
Authors: Ludovici Matteo , Kozul Nina , Materazzi Stefano , Risoluti Roberta , Picardo Mauro , Camera Emanuela
Published: July 2018

The skin surface lipids (SSL) result from the blending of sebaceous and epidermal lipids, which derive from the sebaceous gland (SG) secretion and the permeability barrier of the stratum corneum (SC), respectively. In humans, the composition of the SSL is distinctive of the anatomical distribution of the SG. Thus, the abundance of sebum biomarkers is consistent with the density of the SG. Limited evidence on the influence that the SG exerts on the SC lipidome is available. We explored the differential amounts of sebaceous and epidermal lipids in areas at different SG density with lipidomics approaches. SC was sampled with adhesive patches from forearm, chest, and forehead of 10 healthy adults (8F, 2M) after mechanical removal of sebum with absorbing paper. Lipid extracts of SC were analysed by HPLC/(-)ESI-TOF-MS. In the untargeted approach, the naïve molecular features extraction algorithm was used to extract meaningful entities. Aligned and normalized data were evaluated by univariate and multivariate statistics. Quantitative analysis of free fatty acids (FFA) and cholesterol sulfate (CHS) was performed by targeted HPLC/(-)ESI-TOF-MS, whereas cholesterol and squalene were quantified by GC-MS. Untargeted approaches demonstrated that the relative abundance of numerous lipid species was distinctive of SC depending upon the different SG density. The discriminating species included FFA, CHS, and ceramides. Targeted analyses confirmed that sebaceous FFA and epidermal FFA were increased and decreased, respectively, in areas at high SG density. CHS and squalene, which are biomarkers of epidermal and sebaceous lipid matrices, respectively, were both significantly higher in areas at elevated SG density. Overall, results indicated that the SG secretion intervenes in shaping the lipid composition of the epidermal permeability barrier.
Direct nucleophilic trifluoromethylation of carbonyl compounds by potent greenhouse gas, fluoroform: Improving the reactivity of anionoid trifluoromethyl species in glymes
Authors: Saito Takuya , Wang Jiandong , Tokunaga Etsuko , Tsuzuki Seiji , Shibata Norio
Published: July 2018

A simple protocol to overcome the problematic trifluoromethylation of carbonyl compounds by the potent greenhouse gas “HFC-23, fluoroform” with a potassium base is described. Simply the use of glymes as a solvent or an additive dramatically improves the yields of this transformation. Experimental results and DFT calculations suggest that the beneficial effect deals with glyme coordination to the K+ to produce [K(polyether)n]+ whose diminished Lewis acidity renders the reactive anionoid CF3 counterion species more ‘naked’, thereby slowing down its undesirable decomposition to CF2 and F− and simultaneously increasing its reactivity towards the organic substrate.
Impacts of hatchery-reared mandarin fish Siniperca chuatsi stocking on wild fish community and water quality in a shallow Yangtze lake
Authors: Li Wei , Hicks Brendan J. , Lin Mingli , Guo Chuanbo , Zhang Tanglin , Liu Jiashou , Li Zhongjie , Beauchamp David A.
Published: July 2018

Mandarin fishSiniperca chuatsi, a valuable piscivorous fish, have been stocked into many lakes in China since the 1990s. This study did the first attempt to evaluate the ecological effects of hatchery-reared mandarin fish stocking in the Yangtze River basin lakes. Our study demonstrated a significant change in fish community composition after mandarin fish stocking, but no fish extinction was observed. No significant difference was observed in the total density of 13 forage fish before and after mandarin fish stocking, but the total biomass showed a significant decline after mandarin fish stocking. Significant differences in length-frequency distributions were observed forCarassius auratus,Pseudorasbora parvaandToxabramis swinhoniscaptured before and after stocking mandarin fish. No significant change in habitat distribution was detected before and after mandarin fish stocking. A marked decline in total nitrogen and a slight decline in total phosphorus were observed while a slight increasing trend for Secchi depth was found after stocking. Our findings suggested that mandarin fish stocking can increase predation pressure on forage fish and subsequently optimize the food web structure. Also, mandarin fish stocking has the potential to improve water quality and may be a feasible strategy to alleviate eutrophication of shallow Yangtze lakes.
Age Alters Chromatin Structure and Expression of SUMO Proteins under Stress Conditions in Human Adipose-Derived Stem Cells
Authors: Shan Xiaoyin , Roberts Cleresa , Lan Yemin , Percec Ivona
Published: July 2018

Adult stem cells play a critical role in tissue homeostasis and repair. Aging leads to a decline in stem cells’ regenerative capacity that contributes significantly to the maintenance of organ and tissue functions. Age-dependent genomic and epigenetic modifications together play a role in the disruption of critical cellular pathways. However, the epigenetic mechanisms responsible for the decline of adult stem cell functions remain to be well established. Here, we investigated age-dependent, genome-wide alterations in the chromatin accessibility of primary human adipose-derived stem cells (ASCs) in comparison to age-matched fibroblasts via ATAC-seq technology. Our results demonstrate that aging ASCs possess globally more stable chromatin accessibility profiles as compared to aging fibroblasts, suggesting that robust regulatory mechanisms maintain adult stem cell chromatin structure against aging. Furthermore, we observed age-dependent subtle changes in promoter nucleosome positioning in selective pathways during aging, concurrent with altered small ubiquitin-related modifier (SUMO) protein expression under stress conditions. Together, our data suggest a significant role for nucleosome positioning in sumoylation pathway regulation in stress response during adult stem cell aging. The differences described here between the chromatin structure of human ASCs and fibroblasts will further elucidate the mechanisms regulating gene expression during aging in both stem cells and differentiated cells.
Aggregates of IVIG or Avastin, but not HSA, modify the response to model innate immune response modulating impurities
Authors: Polumuri Swamy Kumar , Haile Lydia A. , Ireland Derek D. C. , Verthelyi Daniela
Published: July 2018

Therapeutic proteins can induce immune responses that affect their safety and efficacy. Product aggregates and innate immune response modulating impurities (IIRMI) are risk factors of product immunogenicity. In this study, we use Intravenous Immunoglobulin (IVIG), Avastin, and Human Serum Albumin (HSA) to explore whether increased aggregates activate innate immune cells or modify the response to IIRMI. We show that increased aggregates (shaken or stirred) in IVIG and Avastin, but not HSA, induced activation of MAPKs (pp38, pERK and pJNK) and transcription of immune-related genes including IL8, IL6, IL1β, CSF1, CCL2, CCL7, CCL3, CCL24, CXCL2, IRAK1, EGR2, CEBPβ, PPARg and TNFSF15 in human PBMC. The immunomodulatory effect was primarily mediated by FcγR, but not by TLR. Interestingly, increased aggregates in IVIG or Avastin magnified innate immune responses to TLR2/4 agonists, but diminished responses to TLR3/9 agonists. This study shows that IIRMI and aggregates can modify the activity of immune cells potentially modifying the milieu where the products are delivered highlighting the complex interplay of different impurities on product immunogenicity risk. Further, we show that aggregates could modify the sensitivity of PBMC-based assays designed to detect IIRMI. Understanding and managing immunogenicity risk is a critical component of product development and regulation.
S100P enhances the motility and invasion of human trophoblast cell lines
Authors: Tabrizi Maral E. A. , Lancaster Tara L. , Ismail Thamir M. , Georgiadou Athina , Ganguly Ankana , Mistry Jayna J. , Wang Keqing , Rudland Philip S. , Ahmad Shakil , Gross Stephane R.
Published: July 2018

S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein’s role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblastsin vivoas well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation.