bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the Healthy Purchase Index (HPI): a scoring system to assess the nutritional quality of household food purchases
Authors: Tharrey Marion , Dubois Christophe , Maillot Matthieu , Vieux Florent , Méjean Caroline , Perignon Marlène , Darmon Nicole
Published: November 2018

Objective

To develop an index to assess the nutritional quality of household food purchases based on food expenditures only.

Design

A database of monthly food purchases of a convenience sample of low-income households was used to develop the Healthy Purchase Index (HPI). The HPI is the sum of two sub-scores based on expenditure shares of food categories in total household food expenditure: the purchase diversity sub-score and the purchase quality sub-score. The first was adapted from an existing diversity score. The second integrated those food categories identified as the best predictors of the nutritional quality of purchases based on associations between expenditure shares of food categories and two nutritional quality indicators: the mean adequacy ratio (MAR) and the mean excess ratio (MER). Correlation between the HPI and a score assessing adherence to French dietary guidelines (PNNS-GSmod) was performed as a first validation.

Setting/Particpants

Food purchases of 112 households from deprived neighbourhoods of Marseille (France), participating in the Opticourses and Jassur projects (2012–2015).

Results

The purchase diversity sub-score reflects the presence in food purchases of five food categories: fruits, vegetables, starches, dairy products, and meat, fish & eggs. The purchase quality sub-score is based on expenditure shares for fruit & vegetables, added fats & seasonings, sweet snacks, cheese, sugary drinks, refined grains and fish, as these were identified as predictors of the nutritional quality of purchases. The HPI was positively associated with the PNNS-GSmod(rs=0·378;P<0·001).

Conclusions

The HPI helps assess the healthiness of household food purchases.
Double Standards: The Role of Gender and Intraparty Politics in Swedish Cabinet Appointments
Authors: Baumann Markus , Bäck Hanna , Davidsson Johan Bo
Published: November 2018

Are female politicians less likely to be promoted to specific ministerial posts, and is it important for them to toe the party line? This article focuses on whether the selection of ministers has a gender-specific dimension. Building on role congruity theory and research showing that female and male politicians are evaluated in a different manner in leadership positions, we present some original hypotheses. For example, we hypothesize that female politicians are less likely to be appointed to cabinet when they have held gender-incongruent committee positions in parliament. We also hypothesize that women are less likely to be appointed to cabinet posts when they have previously deviated from the party line. In an empirical analysis of Swedish ministerial appointments in six cabinets, we find that female politicians were less likely to be appointed to cabinet posts when they have held positions in ‘masculine’ parliamentary committees and when they deviated from the party line in their parliamentary speeches. These results suggest that women are more harshly judged when holding positions that are not in line with traditional gender stereotypes and have important implications for our understanding of gender and political leadership.
Palaeogeography of tropical seasonal coastal wetlands in northern Britain during the early Mississippian Romer's Gap
Authors: MILLWARD David , DAVIES Sarah J. , BRAND Peter J. , BROWNE Michael A. E. , BENNETT Carys E. , KEARSEY Timothy I. , SHERWIN Janet E. , MARSHALL John E. A.
Published: November 2018

The lower Mississippian Ballagan Formation of northern Britain is one of only two successions worldwide to yield the earliest known tetrapods with terrestrial capability following the end-Devonian mass extinction event. Studies of the sedimentary environments and habitats in which these beasts lived have been an integral part of a major research project into how, why and under what circumstances this profound step in the evolution of life on Earth occurred. Here, a new palaeogeographic map is constructed from outcrop data integrated with new and archived borehole material. The map shows the extent of a very low-relief coastal wetland developed along the tropical southern continental margin of Laurussia. Coastal floodplains in the Midland Valley and Tweed basins were separated from the marginal marine seaway of the Northumberland–Solway Basin to the south by an archipelago of more elevated areas. A complex mosaic of sedimentary environments was juxtaposed, and included fresh and brackish to saline and hypersaline lakes, a diverse suite of floodplain palaeosols and a persistent fluvial system in the east of the region. The strongly seasonal climate led to the formation of evaporite deposits alternating with flooding events, both meteoric and marine. Storm surges drove marine floods from the SW into both the western Midland Valley and Northumberland–Solway Basin; marine water also flooded into the Tweed Basin and Tayside in the east. The Ballagan Formation is a rare example in the geological record of a tropical, seasonal coastal wetland that contains abundant, small-scale evaporite deposits. The diverse sedimentary environments and palaeosol types indicate a network of different terrestrial and aquatic habitats in which the tetrapods lived.
Analysis of the Effects on Time Between Divorce Decree and Suicide
Authors: Jamison Ethan C. , Bol Kirk A. , Mintz Sasha N.
Published: November 2018

Abstract. Background: Divorced individuals carry unique suicide risks, from both acute and chronic exposure to stressors from divorce. Aims: Several statewide data sets were linked to assess the relationship between divorce and suicide. Method: Divorced suicide decedents in the Colorado Violent Death Reporting System, 2004–2015, were matched with divorce decree, using multiple identifiers. Statistically significant differences between the linked cohort and all divorced suicide decedents were assessed using chi-square statistics. Kaplan–Meier survival analyses were conducted assessing which demographics and circumstances had a significant effect on the time between divorce and death. Results: The linkage resulted in 381 divorced suicide decedents linked to a divorce decree. Time between divorce and death ranged from less than 1 year to more than 10 years. Age and intimate partner problems both had significant effects on reducing the survival probability at 1 year and beyond. Limitations: Only 14% of divorced suicide decedents were linked to a Colorado divorce decree. There were noted significant differences between the linked cohort and the total divorced suicide population. Conclusion: Better understanding the relationship between divorce and suicide is imperative to design effective prevention programs for this specific population.
The Oxygen Ion Circulation in The Outer Terrestrial Magnetosphere and Its Dependence on Geomagnetic Activity
Authors: Slapak R. , Nilsson H.
Published: November 2018

We have quantified the O+ transports in the plasma sheet and lobes (−20 < XGSM<−10RE) and their dependencies on geomagnetic activity, Kp, using Cluster data. We found that they have similar behavior as the polar region O+ outflow as well as the O+ fluxes in the plasma mantle and high‐latitude dayside magnetosheath, in their response to geomagnetic activity. The sum of the total O+ fluxes in the lobes, plasma sheet, plasma mantle, and high‐latitude magnetosheath equals the O+ outflow above the polar regions for any geomagnetic condition. It can be argued that there are no hidden O+ populations for Cluster, in the sense that there are no significant amounts of O+ with energies outside the energy range of the ion spectrometer, Composition Distribution Function, and/or below the spacecraft potential. Therefore, we have obtained a complete picture of the O+ circulation (and escape) in the outer magnetosphere and its dependence on geomagnetic activity.
Observational Relationship Between Entrainment Rate and Environmental Relative Humidity and Implications for Convection Parameterization
Authors: Lu Chunsong , Sun Cheng , Liu Yangang , Zhang Guang J. , Lin Yanluan , Gao Wenhua , Niu Shengjie , Yin Yan , Qiu Yujun , Jin Lianji
Published: November 2018

Entrainment rate is a critical but highly uncertain quantity in convective parameterizations; especially, the effects of environmental relative humidity on entrainment rate are controversial, or even opposite, in different studies. Analysis of aircraft observations of cumuli from the Routine AAF (Atmospheric Radiation Measurement [ARM] Aerial Facility) Clouds with Low Optical Water Depths (CLOWD) Optical Radiative Observations (RACORO) and Rain in Cumulus over the Ocean (RICO) field campaigns shows that entrainment rate is positively correlated with relative humidity. Physical analysis shows that higher relative humidity promotes entrainment by reducing buoyancy in the cloud cores and by weakening downdrafts near the cloud cores. The reduced buoyancy in the cloud cores and weakened downdrafts surrounding the cores further reduce updrafts in the cloud cores; the cloud cores with smaller updrafts are more significantly affected by their environment, resulting in larger entrainment rate. The relationship between entrainment rate and relative humidity is consistent with the buoyancy sorting concept widely used in convection parameterizations. The results provide reliable in situ observations to improve parameterizations of entrainment rate.
Downscaling of Rainfall Extremes From Satellite Observations
Authors: Zorzetto Enrico , Marani Marco
Published: November 2018

The estimation of the frequency of intense rainfall events is a crucial step for quantifying their impact on human societies and on the environment. This process is hindered by large gaps in ground observational networks at the global scale, such that extensive areas remain ungauged. The increasing availability of satellite‐based rainfall estimates, while providing data with unprecedented resolution and global coverage, also introduces new challenges: the scale disparity between gridded and rain‐gauge precipitation products on the one hand, and the short length of the available satellite records on the other. Here we propose a statistical framework for the estimation of rainfall extremes that is specifically designed to simultaneously address these two key issues, providing a new way of estimating extreme rainfall magnitudes from space. A downscaling procedure is here introduced to recover the spatial correlation and the probability density function of daily rainfall at the point (gauge) scale from coarse‐scale satellite estimates. The results are then combined with a recent statistical model of extremes (the Metastatistical Extreme Value distribution), which optimizes the use of the information obtained from relatively short satellite observational time series. The methodology is tested using data from the Tropical Rainfall Measuring Mission Multisatellite Precipitation Analysis over the Little Washita River, Oklahoma. We find that our approach satisfactorily reproduces downscaled daily rainfall probability density functions and can significantly improve the Tropical Rainfall Measuring Mission Multisatellite Precipitation Analysis‐based estimation of quantiles with return times larger than the length of the available data set (19 years here), which are especially important for several water‐related applications.
Evaluating Soil Resistance Formulations in Thermal‐Based Two‐Source Energy Balance (TSEB) Model: Implications for Heterogeneous Semiarid and Arid Regions
Authors: Li Yan , Kustas William P. , Huang Chunlin , Nieto Hector , Haghighi Erfan , Anderson Martha C. , Domingo Francisco , Garcia Monica , Scott Russell L.
Published: November 2018

Relatively small fluctuations in the surface energy balance and evapotranspiration in semiarid and arid regions can be indicative of significant changes to ecosystem health. Therefore, it is imperative to have approaches for monitoring surface fluxes in these regions. The remote sensing‐based two‐source energy balance (TSEB) model is a suitable method for flux estimation over sparsely vegetated semiarid and arid landscapes since it explicitly considers surface energy flux contributions from soil and vegetation. However, previous studies indicate that TSEB generally underestimates sensible heat flux (H) and hence overestimates latent heat flux (LE) or evapotranspiration for these regions unless soil resistance coefficients are modified based on additional ground information. In this study, TSEB is applied over semiarid and arid regions on three continents using the original soil resistance formulation with modified coefficients and a recently developed physically based soil resistance formulation. Model sensitivity analysis demonstrates the high sensitivity of TSEB with original soil resistance formulation to soil resistance coefficients, while TSEB with the new soil resistance formulation has relatively low sensitivity to uncertainties in all coefficients. The performance of TSEB using different soil resistance formulations is evaluated by comparing modeled H against eddy covariance measurements in six semiarid and arid study sites and ranking the error statistics. Our results indicate that incorporating the new soil resistance formulation into TSEB would enhance its utility in flux estimation over heterogeneous landscapes by obviating its reliance on semiempirical coefficients and thus provide more robust fluxes over sparsely vegetated regions without model calibration and/or parameter tuning.
Impact of Dynamically Changing Discharge on Hyporheic Exchange Processes Under Gaining and Losing Groundwater Conditions
Authors: Wu Liwen , Singh Tanu , Gomez‐Velez Jesus , Nützmann Gunnar , Wörman Anders , Krause Stefan , Lewandowski Jörg
Published: November 2018

Channel discharge, geomorphological setting, and regional groundwater flow determine the spatiotemporal variability of bedform‐induced hyporheic exchange and the emergence of biogeochemical hot spots and hot moments that it drives. Of particular interest, and significantly understudied, is the role that dynamically changing discharge has on the hyporheic exchange process and how regional groundwater flow modulates the effects of transience. In this study, we use a reduced‐complexity model to systematically explore the bedform‐induced hyporheic responses to dynamically changing discharge events in systems with different bedform geometries exposed to varying degrees of groundwater flow (under both upwelling and downwelling conditions). With this in mind, we define metrics to quantify the effects of transience: spatial extent of the hyporheic zone, net hyporheic flux, mean residence time, and denitrification efficiency. We find that regional groundwater flow and geomorphological settings greatly modulate the temporal evolution of bedform‐induced hyporheic responses driven by a single‐peak discharge event. Effects of transience diminish with increasing groundwater upwelling or downwelling fluxes, decreasing bedform aspect ratios, and decreasing channel slopes. Additionally, we notice that increasing discharge intensities can reduce the modulating impacts of regional groundwater flow on the effects of transience but hardly overcomes the geomorphological controls. These findings highlight the necessities of evaluating hyporheic exchange processes in a more comprehensive framework.
Calcimimetic restores diabetic peripheral neuropathy by ameliorating apoptosis and improving autophagy
Authors: Chung You Chul , Lim Ji Hee , Oh Hyun Mi , Kim Hyung Wook , Kim Min Young , Kim Eun Nim , Kim Yaeni , Chang Yoon Sik , Kim Hye Won , Park Cheol Whee
Published: November 2018

Decreased AMPK-eNOS bioavailability mediates the development of diabetic peripheral neuropathy (DPN) through increased apoptosis and decreased autophagy activity in relation to oxidative stress. Schwann cells are responsible for maintaining structural and functional integrity of neurons and for repairing damaged nerves. We evaluated the neuro-protective effect of cinacalcet on DPN by activating the AMPK-eNOS pathway using db/db mice and human Schwann cells (HSCs). Sciatic nerve of db/db mice was characterized by disorganized myelin, axonal shrinkage, and degeneration that were accompanied by marked fibrosis, inflammation, and apoptosis. These phenotypical alterations were significantly improved by cinacalcet treatment along with improvement in sensorimotor functional parameters. Cinacalcet demonstrated favorable effects through increased expression and activation of calcium-sensing receptor (CaSR)-CaMKKβ and phosphorylation of AMPK-eNOS signaling in diabetic sciatic nerve. Cinacalcet decreased apoptosis and increased autophagy activity in relation to decreased oxidative stress in HSCs cultured in high-glucose medium as well. This was accompanied by increased expression of the CaSR, intracellular Ca++ ([Ca++]i) levels, and CaMKKβ-LKB1-AMPK signaling pathway, resulting in the net effect of increased eNOS phosphorylation, NOx concentration, Bcl-2/Bax ratio, beclin 1, and LC3-II/LC3-I ratio. These results demonstrated that cinacalcet treatment ameliorates inflammation, apoptosis, and autophagy through increased expression of the CaSR, [Ca++]i levels and subsequent activation of CaMKKβ-LKB-1-AMPK-eNOS pathway in the sciatic nerve and HSCs under diabetic condition. Therefore, cinacalcet may play an important role in the restoration and amelioration of DPN by ameliorating apoptosis and improving autophagy.
Reply to ‘Dissimilarity measures affected by richness differences yield biased delimitations of biogeographic realms’
Authors: Costello Mark J. , Tsai Peter , Cheung Alan Kwok Lun , Basher Zeenatul , Chaudhary Chhaya
Published: November 2018

Recently, we classified the oceans into 30 biogeographic realms based on species’ endemicity. Castro-Insua et al. criticize the choices of dissimilarity coefficients and clustering approaches used in our paper, and reanalyse the data using alternative techniques. Here, we explain how the approaches used in our original paper yield results in line with existing biogeographical knowledge and are robust to alternative methods of analysis. We also repeat the analysis using several similarity coefficients and clustering algorithms, and a neural network theory method. Although each combination of methods produces outputs differing in detail, the overall pattern of realms is similar. The coarse nature of the present boundaries of the realms reflects the limited field data but may be improved with additional data and mapping to environmental variables.
Real-time assembly of ribonucleoprotein complexes on nascent RNA transcripts
Authors: Duss Olivier , Stepanyuk Galina A. , Grot Annette , O’Leary Seán E. , Puglisi Joseph D. , Williamson James R.
Published: November 2018

Cellular protein-RNA complexes assemble on nascent transcripts, but methods to observe transcription and protein binding in real time and at physiological concentrations are not available. Here, we report a single-molecule approach based on zero-mode waveguides that simultaneously tracks transcription progress and the binding of ribosomal protein S15 to nascent RNA transcripts during early ribosome biogenesis. We observe stable binding of S15 to single RNAs immediately after transcription for the majority of the transcripts at 35 °C but for less than half at 20 °C. The remaining transcripts exhibit either rapid and transient binding or are unable to bind S15, likely due to RNA misfolding. Our work establishes the foundation for studying transcription and its coupled co-transcriptional processes, including RNA folding, ligand binding, and enzymatic activity such as in coupling of transcription to splicing, ribosome assembly or translation.
Degassing-induced fractionation of multiple sulphur isotopes unveils post-Archaean recycled oceanic crust signal in hotspot lava
Authors: Beaudry Patrick , Longpré Marc-Antoine , Economos Rita , Wing Boswell A. , Bui Thi Hao , Stix John
Published: November 2018

Mantle source regions feeding hotspot volcanoes likely contain recycled subducted material. Anomalous sulphur (S) isotope signatures in hotspot lavas have tied ancient surface S to this deep geological cycle, but their potential modification by shallow magmatic processes has generally been overlooked. Here we present S isotope measurements in magmatic sulphides, silicate melt inclusions and matrix glasses from the recent eruption of a hotspot volcano at El Hierro, Canary Islands, which show that degassing induces strongly negative δ34S fractionation in both silicate and sulphide melts. Our results reflect the complex interplay among redox conditions, S speciation and degassing. The isotopic fractionation is mass dependent (Δ33S = 0‰), thus lacking evidence for the recycled Archaean crust signal recently identified at other hotspot volcanoes. However, the source has an enriched signature (δ34S ~ + 3‰), which supports the presence of younger 34S-rich recycled oceanic material in the Canary Island mantle plume.
Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections
Authors: Ackermann Mania , Kempf Henning , Hetzel Miriam , Hesse Christina , Hashtchin Anna Rafiei , Brinkert Kerstin , Schott Juliane Wilhelmine , Haake Kathrin , Kühnel Mark Philipp , Glage Silke , Figueiredo Constanca , Jonigk Danny , Sewald Katherina , Schambach Axel , Wronski Sabine , Moritz Thomas , Martin Ulrich , Zweigerdt Robert , Munder Antje , Lachmann Nico
Published: November 2018

The increasing number of severe infections with multi-drug-resistant pathogens worldwide highlights the need for alternative treatment options. Given the pivotal role of phagocytes and especially alveolar macrophages in pulmonary immunity, we introduce a new, cell-based treatment strategy to target bacterial airway infections. Here we show that the mass production of therapeutic phagocytes from induced pluripotent stem cells (iPSC) in industry-compatible, stirred-tank bioreactors is feasible. Bioreactor-derived iPSC-macrophages (iPSC-Mac) represent a highly pure population of CD45+CD11b+CD14+CD163+ cells, and share important phenotypic, functional and transcriptional hallmarks with professional phagocytes, however with a distinct transcriptome signature similar to primitive macrophages. Most importantly, bioreactor-derived iPSC-Mac rescue mice from Pseudomonas aeruginosa-mediated acute infections of the lower respiratory tract within 4-8 h post intra-pulmonary transplantation and reduce bacterial load. Generation of specific immune-cells from iPSC-sources in scalable stirred-tank bioreactors can extend the field of immunotherapy towards bacterial infections, and may allow for further innovative cell-based treatment strategies.
Coincident molecular auxeticity and negative order parameter in a liquid crystal elastomer
Authors: Mistry D. , Connell S. D. , Mickthwaite S. L. , Morgan P. B. , Clamp J. H. , Gleeson H. F.
Published: November 2018

Auxetic materials have negative Poisson’s ratios and so expand rather than contract in one or several direction(s) perpendicular to applied extensions. The auxetics community has long sought synthetic molecular auxetics – non-porous, inherently auxetic materials which are simple to fabricate and avoid porosity-related weakening. Here, we report, synthetic molecular auxeticity for a non-porous liquid crystal elastomer. For strains above ~0.8 applied perpendicular to the liquid crystal director, the liquid crystal elastomer becomes auxetic with the maximum negative Poisson’s ratio measured to date being -0.74 ± 0.03 – larger than most values seen in naturally occurring molecular auxetics. The emergence of auxeticity coincides with the liquid crystal elastomer backbone adopting a negative order parameter, QB = -0.41 ± 0.01 – further implying negative liquid crystal ordering. The reported behaviours consistently agree with theoretical predictions from Warner and Terentjev liquid crystal elastomer theory. Our results open the door for the design of synthetic molecular auxetics.
X-ray rheography uncovers planar granular flows despite non-planar walls
Authors: Baker James , Guillard François , Marks Benjy , Einav Itai
Published: November 2018

Extremely useful techniques exist to observe the interior of deforming opaque materials, but these methods either require that the sample is replaced with a model material or that the motion is stopped intermittently. For example, X-ray computed tomography cannot measure the continuous flow of materials due to the significant scanning time required for density reconstruction. Here we resolve this technological gap with an alternative X-ray method that does not require such tomographs. Instead our approach uses correlation analysis of successive high-speed radiographs from just three directions to directly reconstruct three-dimensional velocities. When demonstrated on a steady granular system, we discover a compressible flow field that has planar streamlines despite curved confining boundaries, in surprising contrast to Newtonian fluids. More generally, our new X-ray technique can be applied using synchronous source/detector pairs to investigate transient phenomena in various soft matter such as biological tissues, geomaterials and foams.
Observation of non-locality sharing among three observers with one entangled pair via optimal weak measurement
Authors: Hu Meng-Jun , Zhou Zhi-Yuan , Hu Xiao-Min , Li Chuan-Feng , Guo Guang-Can , Zhang Yong-Sheng
Published: November 2018

Bell non-locality plays a fundamental role in quantum theory. Numerous tests of the Bell inequality have been reported as the ground-breaking discovery of the Bell theorem. Up to now, however, most discussions of the Bell scenario have focused on a single pair of entangled particles distributed to only two separated observers. Recently, it has been shown surprisingly that multiple observers can share the non-locality from an entangled pair using the method of weak measurement without post-selection [Phys. Rev. Lett. 114, 250401 (2015)]. Here we report an observation of double CHSH-Bell inequality violations for a single pair of entangled photons with strength continuous-tunable optimal weak measurement in a photonic system. Our results shed new light on the interplay between non-locality and quantum measurements and our design of weak measurement protocol may also be significant for important applications such as unbounded randomness certification and quantum steering.
High density Huh7.5 cell hollow fiber bioreactor culture for high-yield production of hepatitis C virus and studies of antivirals
Authors: Pihl Anne F. , Offersgaard Anna F. , Mathiesen Christian K. , Prentoe Jannick , Fahnøe Ulrik , Krarup Henrik , Bukh Jens , Gottwein Judith M.
Published: November 2018

Chronic hepatitis C virus (HCV) infection poses a serious global public health burden. Despite the recent development of effective treatments there is a large unmet need for a prophylactic vaccine. Further, antiviral resistance might compromise treatment efficiency in the future. HCV cell culture systems are typically based on Huh7 and derived hepatoma cell lines cultured in monolayers. However, efficient high cell density culture systems for high-yield HCV production and studies of antivirals are lacking. We established a system based on Huh7.5 cells cultured in a hollow fiber bioreactor in the presence or absence of bovine serum. Using an adapted chimeric genotype 5a virus, we achieved peak HCV infectivity and RNA titers of 7.6 log10FFU/mL and 10.4 log10IU/mL, respectively. Bioreactor derived HCV showed high genetic stability, as well as buoyant density, sensitivity to neutralizing antibodies AR3A and AR4A, and dependency on HCV co-receptors CD81 and SR-BI comparable to that of HCV produced in monolayer cell cultures. Using the bioreactor platform, treatment with the NS5A inhibitor daclatasvir resulted in HCV escape mediated by the NS5A resistance substitution Y93H. In conclusion, we established an efficient high cell density HCV culture system with implications for studies of antivirals and vaccine development.
Electrophysiological measurement of ion channels on plasma/organelle membranes using an on-chip lipid bilayer system
Authors: Kamiya Koki , Osaki Toshihisa , Nakao Kenji , Kawano Ryuji , Fujii Satoshi , Misawa Nobuo , Hayakawa Masatoshi , Takeuchi Shoji
Published: November 2018

Ion channels are located in plasma membranes as well as on mitochondrial, lysosomal, and endoplasmic reticulum membranes. They play a critical role in physiology and drug targeting. It is particularly challenging to measure the current mediated by ion channels in the lysosomal and the endoplasmic reticulum membranes using the conventional patch clamp method. In this study, we show that our proposed device is applicable for an electrophysiological measurement of various types of ion channel in plasma and organelle membranes. We designed an on-chip device that can form multiple electrical contacts with a measurement system when placed on a mount system. Using crude cell membranes containing ion channels extracted from cultured cells without detergents, we detected open/close signals of the hERG, TRPV1, and NMDA channels on plasma membranes, those of the TRPML1 channels on lysosomal membranes, and open/close signals of the RyR channels on SR membranes. This method will provide a highly versatile drug screening system for ion channels expressed by various cell membranes, including plasma, SR, mitochondrial, Golgi, and lysosomal membranes.
Identification of Immune Signatures of Novel Adjuvant Formulations Using Machine Learning
Authors: Chaudhury Sidhartha , Duncan Elizabeth H. , Atre Tanmaya , Storme Casey K. , Beck Kevin , Kaba Stephen A. , Lanar David E. , Bergmann-Leitner Elke S.
Published: November 2018

Adjuvants have long been critical components of vaccines, but the exact mechanisms of their action and precisely how they alter or enhance vaccine-induced immune responses are often unclear. In this study, we used broad immunoprofiling of antibody, cellular, and cytokine responses, combined with data integration and machine learning to gain insight into the impact of different adjuvant formulations on vaccine-induced immune responses. A Self-Assembling Protein Nanoparticles (SAPN) presenting the malarial circumsporozoite protein (CSP) was used as a model vaccine, adjuvanted with three different liposomal formulations: liposome plus Alum (ALFA), liposome plus QS21 (ALFQ), and both (ALFQA). Using a computational approach to integrate the immunoprofiling data, we identified distinct vaccine-induced immune responses and developed a multivariate model that could predict the adjuvant condition from immune response data alone with 92% accuracy (p = 0.003). The data integration also revealed that commonly used readouts (i.e. serology, frequency of T cells producing IFN-γ, IL2, TNFα) missed important differences between adjuvants. In summary, broad immune-profiling in combination with machine learning methods enabled the reliable and clear definition of immune signatures for different adjuvant formulations, providing a means for quantitatively characterizing the complex roles that adjuvants can play in vaccine-induced immunity. The approach described here provides a powerful tool for identifying potential immune correlates of protection, a prerequisite for the rational pairing of vaccines candidates and adjuvants.
High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3
Authors: Gandhi Amit K. , Kim Walter M. , Sun Zhen-Yu J. , Huang Yu-Hwa , Bonsor Daniel A. , Sundberg Eric J. , Kondo Yasuyuki , Wagner Gerhard , Kuchroo Vijay K. , Petsko Gregory , Blumberg Richard S.
Published: November 2018

T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) is an important immune regulator. Here, we describe a novel high resolution (1.7 Å) crystal structure of the human (h)TIM-3 N-terminal variable immunoglobulin (IgV) domain with bound calcium (Ca++) that was confirmed by nuclear magnetic resonance (NMR) spectroscopy. Significant conformational differences were observed in the B-C, C′-C″ and C′-D loops of hTIM-3 compared to mouse (m)TIM-3, hTIM-1 and hTIM-4. Further, the conformation of the C-C′ loop of hTIM-3 was notably different from hTIM-4. Consistent with the known metal ion-dependent binding of phosphatidylserine (PtdSer) to mTIM-3 and mTIM-4, the NMR spectral analysis and crystal structure of Ca++-bound hTIM-3 revealed that residues in the hTIM-3 F-G loop coordinate binding to Ca++. In addition, we established a novel biochemical assay to define hTIM-3 functionality as determined by binding to human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1). These studies provide new insights useful for understanding and targeting hTIM-3.
Discrimination of contagious and environmental strains of Streptococcus uberis in dairy herds by means of mass spectrometry and machine-learning
Authors: Esener Necati , Green Martin J. , Emes Richard D. , Jowett Benjamin , Davies Peers L. , Bradley Andrew J. , Dottorini Tania
Published: November 2018

Streptococcus uberis is one of the most common pathogens of clinical mastitis in the dairy industry. Knowledge of pathogen transmission route is essential for the selection of the most suitable intervention. Here we show that spectral profiles acquired from clinical isolates using matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) can be used to implement diagnostic classifiers based on machine learning for the successful discrimination of environmental and contagious S. uberis strains. Classifiers dedicated to individual farms achieved up to 97.81% accuracy at cross-validation when using a genetic algorithm, with Cohen’s kappa coefficient of 0.94. This indicates the potential of the proposed methodology to successfully support screening at the herd level. A global classifier developed on merged data from 19 farms achieved 95.88% accuracy at cross-validation (kappa 0.93) and 70.67% accuracy at external validation (kappa 0.34), using data from another 10 farms left as holdout. This indicates that more work is needed to develop a screening solution successful at the population level. Significant MALDI-TOF spectral peaks were extracted from the trained classifiers. The peaks were found to correspond to bacteriocin and ribosomal proteins, suggesting that immunity, growth and competition over nutrients may be correlated to the different transmission routes.
Selection and Validation of Novel RT-qPCR Reference Genes under Hormonal Stimuli and in Different Tissues of Santalum album
Authors: Yan Haifeng , Zhang Yueya , Xiong Yuping , Chen Qingwei , Liang Hanzhi , Niu Meiyun , Guo Beiyi , Li Mingzhi , Zhang Xinhua , Li Yuan , Teixeira da Silva Jaime A. , Ma Guohua
Published: November 2018

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a widely used technique to investigate gene expression levels due to its high throughput, specificity, and sensitivity. An appropriate reference gene is essential for RT-qPCR analysis to obtain accurate and reliable results. To date, no reliable reference gene has been validated for the economically tropical tree, sandalwood (Santalum albumL.). In this study, 13 candidate reference genes, including 12 novel putative reference genes selected from a large set ofS.albumtranscriptome data, as well as the currently used β-actin gene (ACT), were validated in different tissues (stem, leaf, root and callus), as well as callus tissue under salicylic acid (SA), jasmonic acid methyl ester (MeJA), and gibberellin (GA) treatments using geNorm, NormFinder, BestKeeper, Delta Ct and comprehensive RefFinder algorithms. Several novel candidate reference genes were much more stable than the currently used traditional geneACT.ODDpaired withFbp1for SA treatment,CSAandFbp3for MeJA treatment,PP2CandFbp2for GA treatment, as well asFbp1combined withFbp2for the total of three hormone treatments were the most accurate reference genes, respectively.FAB1A, when combined withPP2C, was identified as the most suitable reference gene combination for the four tissues tested, while the combination ofHLMt,PPRandFAB1Awere the most optimal reference genes for all of the experimental samples. In addition, to verify our results, the relative expression level of theSaSSygene was evaluated by the validated reference genes and their combinations in the threeS.albumtissues and under MeJA treatment. The evaluated reference genes in this study will improve the accuracy of RT-qPCR analysis and will benefitS.albumfunctional genomics studies in different tissues and under hormone stimuli in the future.
Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs
Authors: Nalli Ancy D. , Brown Lauren E. , Thomas Cheryl L. , Sayers Thomas J. , Porco John A. , Henrich Curtis J.
Published: November 2018

Rocaglamide has been reported to sensitize several cell types to TRAIL-induced apoptosis. In recent years, advances in synthetic techniques have led to generation of novel rocaglamide analogs. However, these have not been extensively analyzed as TRAIL sensitizers, particularly in TRAIL-resistant renal cell carcinoma cells. Evaluation of rocaglamide and analogs identified 29 compounds that are able to sensitize TRAIL-resistant ACHN cells to TRAIL-induced, caspase-dependent apoptosis with sub-µM potency which correlated with their potency as protein synthesis inhibitors and with loss of cFLIP protein in the same cells. Rocaglamide alone induced cell cycle arrest, but not apoptosis. Rocaglates averaged 4–5-fold higher potency as TRAIL sensitizers than as protein synthesis inhibitors suggesting a potential window for maximizing TRAIL sensitization while minimizing effects of general protein synthesis inhibition. A wide range of other rocaglate effects (e.g. on JNK or RAF-MEK-ERK signaling, death receptor levels, ROS, ER stress, eIF4E phosphorylation) were assessed, but did not contribute to TRAIL sensitization. Other than a rapid loss of MCL-1, rocaglates had minimal effects on mitochondrial apoptotic pathway proteins. The identification of structurally diverse/mechanistically similar TRAIL sensitizing rocaglates provides insights into both rocaglate structure and function and potential further development for use in RCC-directed combination therapy.
Mechanisms of fitness cost reduction for rifampicin-resistant strains with deletion or duplication mutations in rpoB
Authors: Brandis Gerrit , Hughes Diarmaid
Published: November 2018

Rifampicin resistance (RifR) is caused by mutations in rpoB, encoding the β-subunit of RNA polymerase. RifR mutations generally incur a fitness cost and in resistant isolates are frequently accompanied by compensatory mutations in rpoA, rpoB or rpoC. Previous studies of fitness compensation focused on RifR caused by amino acid substitutions within rpoB. RifR is also caused by deletion and duplication mutations in rpoB but it is not known whether or how such mutants can ameliorate their fitness costs. Using experimental evolution of Salmonella carrying RifR deletion or duplication mutations we identified compensatory amino acid substitution mutations within rpoA, rpoB or rpoC in 16 of 21 evolved lineages. Additionally, we found one lineage where a large deletion was compensated by duplication of adjacent amino acids (possibly to fill the gap within the protein structure), two lineages where mutations occurred outside of rpoABC, and two lineages where a duplication mutant reverted to the wild-type sequence. All but the two revertant mutants maintained the RifR phenotype. These data suggest that amino acid substitution mutations are the major compensatory mechanism regardless of the nature of the primary RifR mutation.
Author Correction: HIV-1 Transmissions Among Recently Infected Individuals in Southwest China are Predominantly Derived from Circulating Local Strains
Authors: Li Jianjun , Feng Yi , Shen Zhiyong , Li Yingxin , Tang Zhenzhu , Xiong Runsong , Zhang Hongman , Wei Jing , Zhou Xinjuan , Deng Yueqin , Fang Ningye , Lan Guanghua , Liang Shujia , Zhu Qiuying , Xing Hui , Ruan Yuhua , Shao Yiming
Published: November 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Signal quality of simultaneously recorded endovascular, subdural and epidural signals are comparable
Authors: John Sam E. , Opie Nicholas L. , Wong Yan T. , Rind Gil S. , Ronayne Stephen M. , Gerboni Giulia , Bauquier Sebastien H. , O’Brien Terence J. , May Clive N. , Grayden David B. , Oxley Thomas J.
Published: November 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Rapid through-container detection of fake spirits and methanol quantification with handheld Raman spectroscopy
Authors: Ellis D. I. , Muhamadali H. , Xu Y. , Eccles R. , Goodall I. , Goodacre R.
Published: November 2018

The spirits drinks industry is of significant global economic importance and a major employer worldwide, and the ability to ensure product authenticity and maintain consumer confidence in these high-value products is absolutely essential.
A translational approach to assess the metabolomic impact of stabilized gold nanoparticles by NMR spectroscopy
Authors: Herance José Raul , García Hermenegildo , Gutiérrez-Carcedo Patricia , Navalón Sergio , Pineda-Lucena Antonio , Palomino-Schätzlein Martina
Published: November 2018

The metabolomic impact of gold nanoparticles on a cell model can be modulated by a stabilizer.
Chemometric analysis of integrated FTIR and Raman spectra obtained by non-invasive exfoliative cytology for the screening of oral cancer
Authors: Ghosh Aritri , Raha Sreyan , Dey Susmita , Chatterjee Kabita , Roy Chowdhury Amit , Barui Ananya
Published: November 2018

FTIR spectroscopy and Raman spectroscopy of biological analytes are increasingly explored as screening tools for early detection of cancer.
Optimization of a microchip electrophoresis method with electrochemical detection for the determination of nitrite in macrophage cells as an indicator of nitric oxide production
Authors: Siegel Joseph M. , Schilly Kelci M. , Wijesinghe Manjula B. , Caruso Giuseppe , Fresta Claudia G. , Lunte Susan M.
Published: November 2018

A transient isotachophoresis separation and Pt black working electrode allow detection of nitrite in stimulated macrophage cells with improved sensitivity.
Mobile mass spectrometry for water quality monitoring of organic species present in nuclear waste ponds
Authors: Brkić Boris , Giannoukos Stamatios , Taylor Stephen , Lee Darren F.
Published: November 2018

This work uses a portable mass spectrometer (MS) for lab-based water quality monitoring of organic compounds, which are present in highly toxic nuclear waste ponds.
Highly conductive PEDOT:PSS threaded HKUST-1 thin films
Authors: Li Zhouyi , Guo Yi , Wang Xiaobin , Ying Wen , Chen Danke , Ma Xu , Zhao Xing , Peng Xinsheng
Published: November 2018

A highly conductive and porous PEDOT:PSS threaded HKUST-1 thin film was prepared and utilized as a thin film-like electrode for supercapacitors.
Degradable vinyl copolymers through thiocarbonyl addition–ring-opening (TARO) polymerization
Authors: Bingham Nathaniel M. , Roth Peter J.
Published: November 2018

Radical ring-opening polymerization of a thionolactone gives degradable thioester-functional polymers.
Bi-directional alkyne tandem isomerization via Pd(0)/carboxylic acid joint catalysis: expedient access to 1,3-dienes
Authors: Cera Gianpiero , Lanzi Matteo , Bigi Franca , Maggi Raimondo , Malacria Max , Maestri Giovanni
Published: November 2018

Palladium-hydride catalysis enables dual alkyne isomerisation to conjugated dienes through an operationally simple yet mechanistically challenging route.
Amorphous-to-crystalline transformation toward controllable synthesis of fibrous covalent organic frameworks enabling promotion of proton transport
Authors: Kong Weifu , Jia Wei , Wang Rong , Gong Yifan , Wang Changchun , Wu Peiyi , Guo Jia
Published: November 2018

Reversible imine exchange is adopted to transform amorphous polyazomethine into fibrous crystalline covalent organic frameworks that are able to immobilize Nafion for enhanced proton transport.
Palladium-catalyzed oxidative borylation of conjugated enynones through carbene migratory insertion: synthesis of furyl-substituted alkenylboronates
Authors: Ping Yifan , Chang Taiwei , Wang Kang , Huo Jingfeng , Wang Jianbo
Published: November 2018

A new method for the synthesis of furyl-substituted alkenylboronates has been developed by palladium-catalyzed oxidative borylation reaction of conjugated enynones.
Highlights from the Faraday Discussion 296: quantum effects in small molecular systems, 10–12 September 2018, Edinburgh, United Kingdom
Authors: Ban Loren , Besemer Matthieu , Mouhib Halima
Published: November 2018

Exciting discussions on the impact of quantum effects in small molecular systems took place in the historical city of Edinburgh this fall 2018 in the unique conference format of the Faraday Discussions.
Stereocomplex-affected crystallization behaviour of PDLA in PDLA/PLDLA blends
Authors: Cheng Lu , Hu Cunliang , Li Jingqing , Huang Shaoyong , Jiang Shichun
Published: November 2018

In the presence of SC crystals, the spherulite growth rate of PDLA decreased, whereas its overall crystallization rate increased.
Shear flow simulations of smectic liquid crystals based on the Gay–Berne fluid and the soft sphere string-fluid
Authors: Sarman Sten , Wang Yong-Lei , Laaksonen Aatto
Published: November 2018

Smectic liquid crystal undergoing shear flow.
Deformation mechanisms of polytetrafluoroethylene at the nano- and microscales
Authors: Brownell Matthew , Nair Arun K.
Published: November 2018

Polytetrafluoroethylene (PTFE) coefficient of friction is dependent on a particles density and surface roughness.
Microstructure of ionic liquid (EAN)-rich and oil-rich microemulsions studied by SANS
Authors: Thater Jan C. , Stubenrauch Cosima , Glatter Otto , Klemmer Helge , Sottmann Thomas
Published: November 2018

Role of EAN substructure formation in both oil-in-EAN and EAN-in-oil microemulsions revealed by SANS.
Remarkable pressure-induced emission enhancement based on intermolecular charge transfer in halogen bond-driven dual-component co-crystals
Authors: Li Aisen , Wang Jing , Liu Yingjie , Xu Shuping , Chu Ning , Geng Yijia , Li Bao , Xu Bin , Cui Haining , Xu Weiqing
Published: November 2018

Remarkable pressure-induced emission enhancement from dark to bright based on intermolecular charge transfer (CT) is presented in this study.
X-Ray structure and ionic conductivity studies of anhydrous and hydrated choline chloride and oxalic acid deep eutectic solvents
Authors: Gontrani Lorenzo , Bonomo Matteo , Plechkova Natalia V. , Dini Danilo , Caminiti Ruggero
Published: November 2018

X-Ray, conductivity and molecular dynamics studies shed light on the effect of water of crystallization on choline chloride–oxalic acid DESs
Hydrogel bioelectronics
Authors: Yuk Hyunwoo , Lu Baoyang , Zhao Xuanhe
Published: November 2018

Hydrogels have emerged as a promising bioelectronic interfacing material. This review discusses the fundamentals and recent advances in hydrogel bioelectronics.
Protein engineering through chemical, genetic and computational manipulation
Authors: Hamachi Itaru , Bernardes Gonçalo J. L.
Published: November 2018

Guest editors Itaru Hamachi and Gonçalo Bernardes introduce the Protein Engineering themed issue of Chemical Society Reviews.
Reduced graphene oxide wrap buffering volume expansion of Mn2SnO4 anodes for enhanced stability in lithium-ion batteries
Authors: Cui Lifeng , Li Xing , Yin Chaochuang , Wang Junjie , Li Shasha , Zhang Qiulin , Kang Shifei
Published: November 2018

In this study, Mn2SnO4 nanoparticles@reduced graphene oxide (Mn2SnO4@rGO) composites were prepared using simple steps and applied as high-performance anode materials with good stability for lithium-ion batteries.