bluuebunny/crossref_metadata_2025 huggingface dataset:
MONEY TAXES, MARKET SEGMENTATION, AND SUNSPOT EQUILIBRIA
Authors: Keister Todd
Published: September 2019

This paper investigates how volatile the general price level can be in an equilibrium where all uncertainty is extrinsic. The government operates a lump-sum redistribution policy using fiat money. An approach to modeling asset market segmentation is introduced in which this tax policy determines how volatile the price level can be, which in turn determines the volatility of consumption. The paper characterizes (i) the set of general price levels consistent with the existence of competitive equilibrium and (ii) the resulting set of equilibrium allocations. The results demonstrate how redistribution policies that are fixed in nominal terms can have a destabilizing effect on an economy, and show how to evaluate the amount of volatility that a particular policy may induce.
PREDICTING THE PROBABILITY OF A RECESSION WITH NONLINEAR AUTOREGRESSIVE LEADING-INDICATOR MODELS
Authors: Anderson Heather M. , Vahid Farshid
Published: September 2019

We develop nonlinear leading-indicator models for GDP growth, with the interest-rate spread and growth in M2 as leading indicators. Since policy makers typically are interested in whether a recession is imminent, we evaluate these models according to their ability to predict the probability of a recession. Using data for the United States, we find that conditional on the spread, the marginal contribution of M2 growth in predicting recessions is negligible.
OUT-OF-SAMPLE TESTS FOR GRANGER CAUSALITY
Authors: Chao John , Corradi Valentina , Swanson Norman R.
Published: September 2019

Clive W.J. Granger has summarized his personal viewpoint on testing for causality in numerous articles over the past 30 years and has outlined what he considers to be a useful operational version of his original definition of Granger causality, which he notes is partially alluded to in the Ph.D. dissertation of Norbert Wiener. This operational version of Granger causality is based on a comparison of the one-step-ahead predictive ability of competing models. However, Granger concludes his discussion by noting that it is common practice to test for Granger causality using in-sample F-tests. The practice of using in-sample type Granger causality tests continues to be prevalent. In this paper we develop simple (nonlinear) out-of-sample predictive ability tests of the Granger non-causality null hypothesis. In addition, Monte Carlo experiments are used to investigate the finite sample properites of the test. An empirical illustration shows that the choice of in-sample versus out-of-sample Granger causality tests can crucially affect the conclusions about the predictive content of money for output.
NONLINEAR RISK
Authors: Chauvet Marcelle , Potter Simon
Published: September 2019

This paper analyzes the joint time-series properties of the level and volatility of expected excess stock returns. An unobservable dynamic factor is constructed as a nonlinear proxy for the market risk premia with its first moment and conditional volatility driven by a latent Markov variable. The model allows for the possibility that the risk–return relationship may not be constant across the Markov states or over time. We find an overall negative contemporaneous relationship between the conditional expectation and variance of the monthly value-weighted excess return. However, the sign of the correlation is not stable, but instead varies according to the stage of the business cycle. In particular, around the beginning of recessions, volatility rises substantially, reflecting great uncertainty associated with these periods, while expected return falls, anticipating a decline in earnings. Thus, around economic peaks there is a negative relationship between conditional expectation and variance. However, toward the end of a recession expected return is at its highest value as an anticipation of the economic recovery, and volatility is still very high in anticipation of the end of the contraction. That is, the risk–return relation is positive around business-cycle troughs. This time-varying behavior also holds for noncontemporaneous correlations of these two conditional moments.
TEMPORAL LEONTIEF INVERSE
Authors: Sonis Michael , Hewings Geoffrey J.D.
Published: September 2019

Interest in structural change over time has created a demand for analytical
tools that can assist in exploiting trends and uncover tendencies in
individual sectors or parts of sectors within the context of an economywide
system of accounts. This paper offers an alternative approach and is designed
to be used with annual
input-output or social accounting systems.
To date, analysts have been faced with the prospect of conducting simple
comparative static approaches or the enormity of the task involved in
constructing dynamic models with complex lead and lag structures.
The temporal Leontief inverse, introduced in this paper, offers a less
complex, more tractable method for examining structural change when a time
series of input-output tables is available.
The method draws upon some earlier work that proposed the notion of a field
of influence of change and explored alternative methods of decomposition of
change.
SUPERNEUTRALITY OF MONEY IN STAGGERED WAGE-SETTING MODELS
Authors: Ascari Guido
Published: September 2019

Staggered wage setting is introduced in a dynamic general-equilibrium
monetary model, and the issue of superneutrality of money is addressed.
This paper demonstrates that, in an optimizing framework, a
mild permanent change in the rate of growth of money could have
substantial effects on the steady-state aggregate level of output and
welfare. Previous works fail to reproduce these results because they
consider restrictively simple utility and production functions. The
model exhibits high costs of inflation and provides
a rationale for the pursuit of price stability observed in western countries.
Therefore, in the presence of staggered adjustment, superneutrality of
money proves to be a key issue, which should be taken into account in
any economic model with staggered adjustment.
A qualitative study to understand parent and physician perspectives about cow’s milk fat for children
Authors: Vanderhout Shelley M , Juando-Prats Clara , Birken Catherine S , Thorpe Kevin E , Maguire Jonathon L
Published: September 2019

Objective:

Consensus guidelines recommend that children consume reduced-fat (0·1–2 %) cow’s milk at age 2 years to reduce the risk of obesity. Behaviours and perspectives of parents and physicians about cow’s milk fat for children are unknown. Objectives were to: (i) understand what cow’s milk fat recommendations physicians provide to 2-year-old children; (ii) assess the acceptability of reduced-fat v. whole cow’s milk in children’s diets by parents and physicians; and (iii) explore attitudes and perceptions about cow’s milk fat for children.

Design:

Online questionnaires and individual interviews were conducted. Questionnaire data were analysed using descriptive statistics. Interview transcripts were analysed using a general inductive approach and thematic analysis.

Setting:

The TARGet Kids! practice-based research network in Toronto, Canada.

Participants:

Questionnaire respondents included fifty parents and fifteen physicians; individual interviews were conducted with with fourteen parents and twelve physicians.

Results:

Physicians provided various milk fat recommendations for 2-year-old children. Parents also provided different cow’s milks: eighteen (36 %) provided whole milk and twenty-nine (58 %) provided reduced-fat milk. Analysis of qualitative interviews revealed three themes: (i) healthy eating behaviours, (ii) trustworthy nutrition information and (iii) importance of dietary fat for children.

Conclusions:

Parents provide, and physicians recommend, a variety of cow’s milks for children and hold mixed interpretations of the role of cow’s milk fat in children’s diets. Clarity about its effect on child adiposity is needed to help make informed decisions about cow’s milk fat for children.
Carrier-Transport Study of Gallium Arsenide Hillock Defects
Authors: Xiao Chuanxiao , Jiang Chun-Sheng , Liu Jun , Norman Andrew , Moseley John , Schulte Kevin , Ptak Aaron J. , Gorman Brian , Al-Jassim Mowafak , Haegel Nancy M. , Moutinho Helio
Published: September 2019

Single-crystalline gallium arsenide (GaAs) grown by various techniques can exhibit hillock defects on the surface when sub-optimal growth conditions are employed. The defects act as nonradiative recombination centers and limit solar cell performance. In this paper, we applied near-field transport imaging to study hillock defects in a GaAs thin film. On the same defects, we also performed near-field cathodoluminescence, standard cathodoluminescence, electron-backscattered diffraction, transmission electron microscopy, and energy-dispersive X-ray spectrometry. We found that the luminescence intensity around the hillock area is two orders of magnitude lower than on the area without hillock defects in the millimeter region, and the excess carrier diffusion length is degraded by at least a factor of five with significant local variation. The optical and transport properties are affected over a significantly larger region than the observed topography and crystallographic and chemical compositions associated with the defect.
DE ZOLT’S POSTULATE: AN ABSTRACT APPROACH
Authors: GIOVANNINI EDUARDO N. , HAEUSLER EDWARD H. , LASSALLE-CASANAVE ABEL , VELOSO PAULO A. S.
Published: September 2019

A theory of magnitudes involves criteria for their equivalence, comparison and addition. In this article we examine these aspects from an abstract viewpoint, by focusing on the so-called De Zolt’s postulate in the theory of equivalence of plane polygons (“If a polygon is divided into polygonal parts in any given way, then the union of all but one of these parts is not equivalent to the given polygon”). We formulate an abstract version of this postulate and derive it from some selected principles for magnitudes. We also formulate and derive an abstract version of Euclid’s Common Notion 5 (“The whole is greater than the part”), and analyze its logical relation to the former proposition. These results prove to be relevant for the clarification of some key conceptual aspects of Hilbert’s proof of De Zolt’s postulate, in his classicalFoundations of Geometry(1899). Furthermore, our abstract treatment of this central proposition provides interesting insights for the development of a well-behaved theory ofcompatiblemagnitudes.
Atrazine induces penis abnormalities including hypospadias in mice
Authors: Govers Luke C. , Harper Alesia P. , Finger Bethany J. , Mattiske Deidre M. , Pask Andrew J. , Green Mark P.
Published: September 2019

Use of the herbicide atrazine (ATR) is banned in the European Union; yet, it is still widely used in the USA and Australia. ATR is known to alter testosterone and oestrogen production and thus reproductive characteristics in numerous species. In this proof of concept study, we examined the effect of ATR exposure, at a supra-environmental dose (5 mg/kg bw/day), beginning on E9.5 in utero, prior to sexual differentiation of the reproductive tissues, until 26 weeks of age, on the development of the mouse penis. Notably, this is the first study to specifically investigate whether ATR can affect penis characteristics. We show that ATR exposure, beginning in utero, causes a shortening (demasculinisation) of penis structures and increases the incidence of hypospadias in mice. These data indicate the need for further studies of ATR on human reproductive development and fertility, especially considering its continued and widespread use.
Prenatal and childhood exposures are associated with thymulin concentrations in young adolescent children in rural Nepal
Authors: Palmer Amanda C. , Schulze Kerry J. , Khatry Subarna K. , West Keith P.
Published: September 2019

The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n= 290; aged 9–13 years) born to participants in a cluster-randomized trial of maternal vitamin A or β-carotene supplementation in rural Nepal (1994–1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (β= 0.02;P= 0.05) and higher concentrations among children born to β-carotene-supplemented mothers (β= 0.19;P< 0.05). At ∼9–12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (β= 0.02;P< 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (β= −0.13;P= 0.15), during the monsoon (β= −0.22;P= 0.04), and pre-harvest (β= −0.34;P= 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.
Oxygen Ion Dynamics in the Earth's Ring Current: Van Allen Probes Observations
Authors: Yue Chao , Bortnik Jacob , Li Wen , Ma Qianli , Wang Chih‐Ping , Thorne Richard M. , Lyons Larry , Reeves Geoffrey D. , Spence Harlan E. , Gerrard Andrew J. , Gkioulidou Matina , Mitchell Donald G.
Published: September 2019

Oxygen (O+) enhancements in the inner magnetosphere are often observed during geomagnetically active times, such as geomagnetic storms. In this study, we quantitatively examine the difference in ring current dynamics with and without a substantial O+ ion population based on almost 6 years of Van Allen Probes observations. Our results have not only confirmed previous finding of the role of O+ ions to the ring current but also found that abundant O+ ions are always present during large storms when sym‐H < −60 nT without exception, while having the pressure ratio (ℛ) between O+ and proton (H+) larger than 0.8 and occasionally even larger than 1 when L < 3. Simultaneously, the pressure anisotropy decreases with decreasing sym‐H and increasing L shell. The pressure anisotropy decrease during the storm main phase is likely related to the pitch angle isotropization processes. In addition, we find that ℛ increases during the storm main phase and then decreases during the storm recovery phase, suggesting faster buildup and decay of O+ pressure compared to H+ ions, which are probably associated with some species dependent source and/or energization as well as loss processes in the inner magnetosphere.
Recognition of Mesoscale Strike‐Slip En Echelon Faults From 2‐D Nonporous Models
Authors: Wong Louis Ngai Yuen , Zhang Yahui
Published: September 2019

Growth and connection of preexisting fractures have been recognized as the driving mechanism of rock fracturing. This paper aims at throwing light on the geological implications of the fracturing behavior in pre‐cracked rock observed in rock mechanics‐oriented experiments, by numerical interpretation on the interaction of en echelon fractures. To properly simulate grain crushing involved in cataclastic deformation of nonporous rocks, a sophisticated numerical scheme incorporating rock morphology and crystallography into the grain‐based model is proposed. In line with a previous experimental study, seven grain‐based models with different configurations of en echelon flaws are numerically tested under uniaxial compression. The key results are (1) evaluation of the influences of preexisting flaws on mechanical properties and damage degree of the host rock, (2) visualization of the microfracture process zone into visible cracks, and (3) generalization of three different patterns of major fracture formation from en echelon fractures, during which the ratio of the number of intergranular to intragranular microcracks is used for evaluation of the cataclastic deformation process and the stress level. Based on the numerical results, we provide valuable interpretation on (1) the field occurrence of strike‐slip fault system with typical fracturing features, focusing on the effects of the sense of left or right stepping and the degrees of separation/overlap of the master fractures, and (2) three different mechanisms of fault formation from preexisting fractures. As an initial attempt to relate rock fracturing observed in laboratory experiments with the field occurrence, capabilities and limitations of this study are also presented.
Allele-specific expression and high-throughput reporter assay reveal functional genetic variants associated with alcohol use disorders
Authors: Rao Xi , Thapa Kriti S. , Chen Andy B. , Lin Hai , Gao Hongyu , Reiter Jill L. , Hargreaves Katherine A. , Ipe Joseph , Lai Dongbing , Xuei Xiaoling , Wang Yue , Gu Hongmei , Kapoor Manav , Farris Sean P. , Tischfield Jay , Foroud Tatiana , Goate Alison M. , Skaar Todd C. , Mayfield R. Dayne , Edenberg Howard J. , Liu Yunlong
Published: September 2019

Genome-wide association studies (GWAS) of complex traits, such as alcohol use disorders (AUD), usually identify variants in non-coding regions and cannot by themselves distinguish whether the associated variants are functional or in linkage disequilibrium with the functional variants. Transcriptome studies can identify genes whose expression differs between alcoholics and controls. To test which variants associated with AUD may cause expression differences, we integrated data from deep RNA-seq and GWAS of four postmortem brain regions from 30 subjects with AUD and 30 controls to analyze allele-specific expression (ASE). We identified 88 genes with differential ASE in subjects with AUD compared to controls. Next, to test one potential mechanism contributing to the differential ASE, we analyzed single nucleotide polymorphisms (SNPs) in the 3′ untranslated regions (3′UTR) of these genes. Of the 88 genes with differential ASE, 61 genes contained 437 SNPs in the 3′UTR with at least one heterozygote among the subjects studied. Using a modified PASSPORT-seq (parallel assessment of polymorphisms in miRNA target-sites by sequencing) assay, we identified 25 SNPs that affected RNA levels in a consistent manner in two neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Many of these SNPs are in binding sites of miRNAs and RNA-binding proteins, indicating that these SNPs are likely causal variants of AUD-associated differential ASE. In sum, we demonstrate that a combination of computational and experimental approaches provides a powerful strategy to uncover functionally relevant variants associated with the risk for AUD.
Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry
Authors: Huang Yu-Kuan , Wang Minyu , Sun Yu , Di Costanzo Natasha , Mitchell Catherine , Achuthan Adrian , Hamilton John A. , Busuttil Rita A. , Boussioutas Alex
Published: September 2019

Tumor-associated macrophages (TAMs), one of the most abundant immune components in gastric cancer (GC), are difficult to characterize due to their heterogeneity. Multiple approaches have been used to elucidate the issue, however, due to the tissue-destructive nature of most of these methods, the spatial distribution of TAMs in situ remains unclear. Here we probe the relationship between tumor context and TAM heterogeneity by multiplex immunohistochemistry of 56 human GC cases. Using distinct expression marker profiles on TAMs, we report seven predominant populations distributed between tumor and non-tumor tissue. TAM population-associated gene signatures reflect their heterogeneity and polarization in situ. Increased density of CD163+ (CD206−) TAMs with concurrent high CD68 expression is associated with upregulated immune-signaling and improved patient survival by univariate, but not multivariate analysis. CD68-only and CD206+ TAMs are correlated with high PDL1 expression.
Mechanical-force-induced non-local collective ferroelastic switching in epitaxial lead-titanate thin films
Authors: Lu Xiaoyan , Chen Zuhuang , Cao Ye , Tang Yunlong , Xu Ruijuan , Saremi Sahar , Zhang Zhan , You Lu , Dong Yongqi , Das Sujit , Zhang Hangbo , Zheng Limei , Wu Huaping , Lv Weiming , Xie Guoqiang , Liu Xingjun , Li Jiangyu , Chen Lang , Chen Long-Qing , Cao Wenwu , Martin Lane W.
Published: September 2019

Ferroelastic switching in ferroelectric/multiferroic oxides plays a crucial role in determining their dielectric, piezoelectric, and magnetoelectric properties. In thin films of these materials, however, substrate clamping is generally thought to limit the electric-field- or mechanical-force-driven responses to the local scale. Here, we report mechanical-force-induced large-area, non-local, collective ferroelastic domain switching in PbTiO3 epitaxial thin films by tuning the misfit-strain to be near a phase boundary wherein c/a and a1/a2 nanodomains coexist. Phenomenological models suggest that the collective, c-a-c-a ferroelastic switching arises from the small potential barrier between the degenerate domain structures, and the large anisotropy of a and c domains, which collectively generates much larger response and large-area domain propagation. Large-area, non-local response under small stimuli, unlike traditional local response to external field, provides an opportunity of unique response to local stimuli, which has potential for use in high-sensitivity pressure sensors and switches.
A dual role of prestimulus spontaneous neural activity in visual object recognition
Authors: Podvalny Ella , Flounders Matthew W. , King Leana E. , Holroyd Tom , He Biyu J.
Published: September 2019

Vision relies on both specific knowledge of visual attributes, such as object categories, and general brain states, such as those reflecting arousal. We hypothesized that these phenomena independently influence recognition of forthcoming stimuli through distinct processes reflected in spontaneous neural activity. Here, we recorded magnetoencephalographic (MEG) activity in participants (N = 24) who viewed images of objects presented at recognition threshold. Using multivariate analysis applied to sensor-level activity patterns recorded before stimulus presentation, we identified two neural processes influencing subsequent subjective recognition: a general process, which disregards stimulus category and correlates with pupil size, and a specific process, which facilitates category-specific recognition. The two processes are doubly-dissociable: the general process correlates with changes in criterion but not in sensitivity, whereas the specific process correlates with changes in sensitivity but not in criterion. Our findings reveal distinct mechanisms of how spontaneous neural activity influences perception and provide a framework to integrate previous findings.
Cyclic two-step electrolysis for stable electrochemical conversion of carbon dioxide to formate
Authors: Lee Chan Woo , Cho Nam Heon , Nam Ki Tae , Hwang Yun Jeong , Min Byoung Koun
Published: September 2019

Pd metal and Pd-based alloys are ideal catalysts that allow for the electrochemical conversion of CO2 to HCOO− at almost zero-overpotential with high selectivity, but catalyst degradation caused by concurrent CO poisoning limits their practical implementation. Here, we demonstrate that cyclic two-step electrolysis, by applying the reduction and oxidation potentials alternately, achieves 100% current density stability and 97.8% selectivity toward HCOO− production for at least 45 h. The key idea for achieving the reliability is based on the selective removal of CO by controlling the parameters during the oxidation step, which utilizes the different reversibility of HCOO− and CO production reactions. Furthermore, it is found that potentiostatic electrolysis causes CO adsorption and subsequent dehydridation, which in turn lowers HCOO− selectivity. Our work provides a system-level strategy for solving the poisoning issue that is inevitable in many electrocatalytic reactions.
Frequency stabilization and noise-induced spectral narrowing in resonators with zero dispersion
Authors: Huang L. , Soskin S. M. , Khovanov I. A. , Mannella R. , Ninios K. , Chan H. B.
Published: September 2019

Mechanical resonators are widely used as precision clocks and sensitive detectors that rely on the stability of their eigenfrequencies. The phase noise is determined by different factors including thermal noise, frequency noise of the resonator and noise in the feedback circuitry. Increasing the vibration amplitude can mitigate some of these effects but the improvements are limited by nonlinearities that are particularly strong for miniaturized micro- and nano-mechanical systems. Here we design a micromechanical resonator with non-monotonic dependence of the eigenfrequency on energy. Near the extremum, where the dispersion of the eigenfrequency is zero, the system regains certain characteristics of a linear resonator, albeit at large amplitudes. The spectral peak undergoes narrowing when the noise intensity is increased. With the resonator serving as the frequency-selecting element in a feedback loop, the phase noise at the extremum amplitude is ~3 times smaller than the minimal noise in the conventional nonlinear regime.
Microscale pH variations during drying of soils and desert biocrusts affect HONO and NH3 emissions
Authors: Kim Minsu , Or Dani
Published: September 2019

Microscale interactions in soil may give rise to highly localised conditions that disproportionally affect soil nitrogen transformations. We report mechanistic modelling of coupled biotic and abiotic processes during drying of soil surfaces and biocrusts. The model links localised microbial activity with pH variations within thin aqueous films that jointly enhance emissions of nitrous acid (HONO) and ammonia (NH3) during soil drying well above what would be predicted from mean hydration conditions and bulk soil pH. We compared model predictions with case studies in which reactive nitrogen gaseous fluxes from drying biocrusts were measured. Soil and biocrust drying rates affect HONO and NH3 emission dynamics. Additionally, we predict strong effects of atmospheric NH3 levels on reactive nitrogen gas losses. Laboratory measurements confirm the onset of microscale pH localisation and highlight the critical role of micro-environments in the resulting biogeochemical fluxes from terrestrial ecosystems.
Adiabatic two-qubit gates in capacitively coupled quantum dot hybrid qubits
Authors: Frees Adam , Mehl Sebastian , Gamble John King , Friesen Mark , Coppersmith S. N.
Published: September 2019

The ability to tune qubits to flat points in their energy dispersions (“sweet spots”) is an important tool for mitigating the effects of charge noise and dephasing in solid-state devices. However, the number of derivatives that must be simultaneously set to zero grows exponentially with the number of coupled qubits, making the task untenable for as few as two qubits. This is a particular problem for adiabatic gates, due to their slower speeds. Here, we propose an adiabatic two-qubit gate for quantum dot hybrid qubits, based on the tunable, electrostatic coupling between distinct charge configurations. We confirm the absence of a conventional sweet spot, but show that controlled-Z (CZ) gates can nonetheless be optimized to have fidelities of ~99% for a typical level of quasistatic charge noise (σε ≃ 1 μeV). We then develop the concept of a dynamical sweet spot (DSS), for which the time-averaged energy derivatives are set to zero, and identify a simple pulse sequence that achieves an approximate DSS for a CZ gate, with a 5× improvement in the fidelity. We observe that the results depend on the number of tunable parameters in the pulse sequence, and speculate that a more elaborate sequence could potentially attain a true DSS.
Logical design of oral glucose ingestion pattern minimizing blood glucose in humans
Authors: Fujii Masashi , Murakami Yohei , Karasawa Yasuaki , Sumitomo Yohei , Fujita Suguru , Koyama Masanori , Uda Shinsuke , Kubota Hiroyuki , Inoue Hiroshi , Konishi Katsumi , Oba Shigeyuki , Ishii Shin , Kuroda Shinya
Published: September 2019

Excessive increase in blood glucose level after eating increases the risk of macroangiopathy, and a method for not increasing the postprandial blood glucose level is desired. However, a logical design method of the dietary ingestion pattern controlling the postprandial blood glucose level has not yet been established. We constructed a mathematical model of blood glucose control by oral glucose ingestion in three healthy human subjects, and predicted that intermittent ingestion 30 min apart was the optimal glucose ingestion patterns that minimized the peak value of blood glucose level. We confirmed with subjects that this intermittent pattern consistently decreased the peak value of blood glucose level. We also predicted insulin minimization pattern, and found that the intermittent ingestion 30 min apart was optimal, which is similar to that of glucose minimization pattern. Taken together, these results suggest that the glucose minimization is achieved by suppressing the peak value of insulin concentration, rather than by enhancing insulin concentration. This approach could be applied to design optimal dietary ingestion patterns.
Flux sampling is a powerful tool to study metabolism under changing environmental conditions
Authors: Herrmann Helena A. , Dyson Beth C. , Vass Lucy , Johnson Giles N. , Schwartz Jean-Marc
Published: September 2019

The development of high-throughput ‘omic techniques has sparked a rising interest in genome-scale metabolic models, with applications ranging from disease diagnostics to crop adaptation. Efficient and accurate methods are required to analyze large metabolic networks. Flux sampling can be used to explore the feasible flux solutions in metabolic networks by generating probability distributions of steady-state reaction fluxes. Unlike other methods, flux sampling can be used without assuming a particular cellular objective. We have undertaken a rigorous comparison of several sampling algorithms and concluded that the coordinate hit-and-run with rounding (CHRR) algorithm is the most efficient based on both run-time and multiple convergence diagnostics. We demonstrate the power of CHRR by using it to study the metabolic changes that underlie photosynthetic acclimation to cold ofArabidopsis thalianaplant leaves. In combination with experimental measurements, we show how the regulated interplay between diurnal starch and organic acid accumulation defines the plant acclimation process. We confirm fumarate accumulation as a requirement for cold acclimation and further predictγ–aminobutyric acid to have a key role in metabolic signaling under cold conditions. These results demonstrate how flux sampling can be used to analyze the feasible flux solutions across changing environmental conditions, whereas eliminating the need to make assumptions which introduce observer bias.
Life cycle progression and sexual development of the apicomplexan parasite Cryptosporidium parvum
Authors: Tandel Jayesh , English Elizabeth D. , Sateriale Adam , Gullicksrud Jodi A. , Beiting Daniel P. , Sullivan Megan C. , Pinkston Brittain , Striepen Boris
Published: September 2019

The apicomplexan parasite Cryptosporidium is a leading global cause of severe diarrhoeal disease and an important contributor to early childhood mortality. Currently, there are no fully effective treatments or vaccines available. Parasite transmission occurs through ingestion of oocysts, through either direct contact or consumption of contaminated water or food. Oocysts are meiotic spores and the product of parasite sex. Cryptosporidium has a single-host life cycle in which both asexual and sexual processes occur in the intestine of infected hosts. Here, we genetically engineered strains of Cryptosporidium to make life cycle progression and parasite sex tractable. We derive reporter strains to follow parasite development in culture and in infected mice and define the genes that orchestrate sex and oocyst formation through mRNA sequencing of sorted cells. After 2 d, parasites in cell culture show pronounced sexualization, but productive fertilization does not occur and infection falters. By contrast, in infected mice, male gametes successfully fertilize female parasites, which leads to meiotic division and sporulation. To rigorously test for fertilization, we devised a two-component genetic-crossing assay using a reporter that is activated by Cre recombinase. Our findings suggest obligate developmental progression towards sex in Cryptosporidium, which has important implications for the treatment and prevention of the infection.
Effects of Photodynamic Therapy with Redaporfin on Tumor Oxygenation and Blood Flow in a Lung Cancer Mouse Model
Authors: Karwicka Malwina , Pucelik Barbara , Gonet Michał , Elas Martyna , Dąbrowski Janusz M.
Published: September 2019

Three photodynamic therapy (PDT) protocols with 15 min, 3 h and 72 h drug-to-light time intervals (DLIs) were performed using a bacteriochlorin named redaporfin, as a photosensitizer. Blood flow and pO2 changes after applying these protocols were investigated in a Lewis lung carcinoma (LLC) mouse model and correlated with long-term tumor responses. In addition, cellular uptake, cytotoxicity and photocytotoxicity of redaporfin in LLC cells were evaluated. Our in vitro tests revealed negligible cytotoxicity, significant cellular uptake, generation of singlet oxygen, superoxide ion and hydroxyl radicals in the cells and changes in the mechanism of cell death as a function of the light dose. Results of in vivo studies showed that treatment focused on vascular destruction (V-PDT) leads to a highly effective long-term antineoplastic response mediated by a strong deprivation of blood supply. Tumors in 67% of the LLC bearing mice treated with V-PDT regressed completely and did not reappear for over 1 year. This significant efficacy can be attributed to photosensitizer (PS) properties as well as distribution and accurate control of oxygen level and density of vessels before and after PDT. V-PDT has a greater potential for success than treatment based on longer DLIs as usually applied in clinical practice.
miR-146a Deficiency Accelerates Hepatic Inflammation Without Influencing Diet-induced Obesity in Mice
Authors: Javidan Aida , Jiang Weihua , Okuyama Michihiro , Thiagarajan Devi , Yang Lihua , Moorleghen Jessica J. , Muniappan Latha , Subramanian Venkateswaran
Published: September 2019

miR-146a, an anti-inflammatory microRNA, is shown to be a negative regulator of adipocyte inflammation. However, the functional contribution of miR-146a in the development of obesity is not defined. In order to determine whether miR-146a influences diet-induced obesity, mice that were either wild type (WT) or miR-146a deficient (KO) were fed with high (60% kcal) fat diet (HFD) for 16 weeks. Deficiency of miR-146a did not influence obesity measured as HFD-induced body weight and fat mass gain, or metabolism of glucose and insulin tolerance. In addition, adipocyte apoptosis, adipose tissue collagen and macrophage accumulation as detected by TUNEL, Picro Sirius and F4/80 immunostaining, respectively, were comparable between the two groups of mice. Although, miR-146a deficiency had no influence on HFD-induced hepatic lipid accumulation, interestingly, it significantly increased obesity-induced inflammatory responses in liver tissue. The present study demonstrates that miR-146a deficiency had no influence on the development of HFD-induced obesity and adipose tissue remodeling, whereas it significantly increased hepatic inflammation in obese mice. This result suggests that miR-146a regulates hepatic inflammation during development of obesity.
The role of anthrax toxin protein receptor 1 as a new mechanosensor molecule and its mechanotransduction in BMSCs under hydrostatic pressure
Authors: Cheng Baixiang , Liu Yanzheng , Zhao Ying , Li Qiang , Liu Yanli , Wang Junjun , Chen Yongjin , Zhang Min
Published: September 2019

Anthrax toxin protein receptor (ANTXR) 1 has many similarities to integrin and is regarded in some respects as a single-stranded integrin protein. However, it is not clear whether ANTXR1 responds to mechanical signals secondary to the activation of integrins or whether it is a completely new, independent and previously undiscovered mechanosensor that responds to an undefined subset of mechanical signaling molecules. Our study demonstrates that ANTXR1 is a novel mechanosensor on the cell membrane, acting independently from the classical mechanoreceptor molecule integrinβ1. We show that bone marrow stromal cells (BMSCs) respond to the hydrostatic pressure towards chondrogenic differentiation partly through the glycogen synthase kinase (GSK) 3β/β-Catenin signaling pathway, which can be partly regulated by ANTXR1 and might be related to the direct binding between ANTXR1 and low-density lipoprotein receptor-related protein (LRP) 5/6. In addition, ANTXR1 specifically activates Smad2 and upregulates Smad4 expression to facilitate the transport of activated Smad2 to the nucleus to regulate chondrogenesis, which might be related to the direct binding between ANTXR1 and Actin/Fascin1. We also demonstrate that ANTXR1 binds to some extent with integrinβ1, but this interaction does not affect the expression and function of either protein under pressure. Thus, we conclude that ANTXR1 plays a crucial role in BMSC mechanotransduction and controls specific signaling pathways that are distinct from those of integrin to influence the chondrogenic responses of BMSCs under hydrostatic pressure.
Annihilating Pores in the Desired Layer of a Porous Silicon Bilayer with Different Porosities for Layer Transfer
Authors: Chiang C.-C. , Lee Benjamin T.-H.
Published: September 2019

A silicon layer that is tens of micrometers thick on a handle substrate is desired for applications involving power devices, microelectromechanical systems (MEMS), highly efficient silicon solar cells (<50 µm), etc. In general, if the initial silicon layer obtained from the layer transfer process using the etch-stop or ion-cut techniques, which may provide very accurate thickness control, is too thin, then additional epitaxial growth is required to increase the thickness of the silicon layer. However, epitaxial growth under strict predeposition conditions is a time-consuming and expensive process. On the other hand, producing porous silicon via anodization in a hydrofluoric acid solution offers an efficient way to control the dimensions of the generated pores directly on the nano- or macroscale via the current density. When sintering the porous layer via high-temperature argon annealing, the porosity of the porous layer determines whether this porous layer can serve as a device layer or a separation layer. In addition, it is clearly easier to create a transferred layer ten of micrometers thick via anodization than by ion implantation and/or epitaxial deposition.
The Association between Body Composition using Dual energy X-ray Absorptiometry and Type-2 Diabetes: A Systematic Review and Meta-Analysis of Observational studies
Authors: Gupta Preeti , Lanca Carla , Gan Alfred T. L. , Soh Pauline , Thakur Sahil , Tao Yijin , Kumari Neelam , Man Ryan E. K. , Fenwick Eva K. , Lamoureux Ecosse L.
Published: September 2019

The association between objective measures of body composition (BC) with type 2 diabetes (T2DM) is inconclusive. We conducted a systematic review and meta-analysis to examine the association between several body composition (BC) indices assessed using dual energy X-ray absorptiometry (DXA), and T2DM. Using PRISMA guidelines, we searched for observational studies investigating BC measures, including total body fat mass (BFM), visceral fat mass (VFM), subcutaneous fat mass (SFM), and fat free mass (FFM); and T2DM. Of 670 titles initially identified, 20 were included. High VFM was consistently associated with T2DM. For every kg increase in VFM, the odds of having T2DM increased by two-fold for males (OR 2.28 [95% CI 1.42 to 3.65], p = 0.001) and more than 4-fold for females (OR 4.24 [1.64 to 11.02], p = 0.003). The presence of T2DM was associated with 2-fold higher odds of low FFM (OR 2.38 [1.44 to 3.95]). We found evidence that greater VFM is a risk factor for prevalent and incident T2DM. While the presence of T2DM is associated with reduced FFM; the relationship between FFM and BFM with T2DM remains unclear. Reducing VFM and increasing FFM through lifestyle changes may reduce the risk of T2DM and mitigate its deleterious effect on BC, respectively.
Characterisation of high molecular weight hop proanthocyanidins using Analytical Ultracentrifugation
Authors: Gadon Arthur , Linforth Robert , Harding Stephen E. , Cook David
Published: September 2019

We report the novel application of Analytical Ultracentrifugation (AUCF) to characterise the polymeric proanthocyanidin fraction of hops. Extraction of hop samples with 70% acetone (aq) followed by a C-18 Solid Phase Extraction yielded polyphenolic fractions for AUCF analysis. Sedimentation velocity experiments demonstrated the presence of discrete molecular weight bands of proanthocyanidins, as opposed to a continuous distribution of molecular weights. There were 4 such bands for Saaz hop (0.15, 1.1, 2.7 and 4.4S) and 3 bands for Magnum (0.15, 1.6 and 3.0S). The method resulted in a reproducible size (sedimentation coefficient) distribution for replicate runs of the same extract and for extracts prepared from different samples of the same hop variety. Sedimentation equilibrium experiments were then used to fit molecular weight distributions using the new SEDFIT-MSTAR method for the same samples. Thus we report for the first time polymeric proanthocyanidins in hops with molecular weights of up to 100 kDa in Saaz hop (or up to 56 kDa in Magnum). This represents the first application of AUCF to characterise complex fractions of polyphenolics extracted from botanical sources and the methodology developed should find wider application in the study of this diverse and bioactive class of compounds.
Estimation of a whole plant Q10 to assess seagrass productivity during temperature shifts
Authors: Rasmusson Lina M. , Gullström Martin , Gunnarsson Pontus C. B. , George Rushingisha , Björk Mats
Published: September 2019

Through respiration and photosynthesis, seagrass meadows contribute greatly to carbon and oxygen fluxes in shallow coastal waters. There is increasing concern about how shallow-water primary producers will react to a near-future climate scenario with increased temperature variation. When modelling primary productivity under high temperature variability, Q10 values are commonly used to predict rate changes depending on biophysical factors. Q10 values are often assumed to be constant and around 2.0 (i.e. a doubling of the rate with a temperature increase of 10 °C). We aimed to establish how the gas exchange of seagrass (Zostera marina) tissues at various maturity stages would respond over a broad range of temperatures. Seagrass shoot maturity stage clearly affected respiration and apparent photosynthesis, and the Q10 results indicated a skewed balance between the two processes, with a higher photosynthetic Q10 during periods of elevated temperatures. When estimating whole-plant Q10 in a realistic maximal temperature range, we found that the overall response of a seagrass plant’s net O2exchange balance can be as much as three to four times higher than under ambient temperatures. Our findings indicate that plant tissue age and temperature should be considered when assessing and modelling carbon and oxygen fluctuations in vegetated coastal areas.
Author Correction: Noninvasive Self-diagnostic Device for Tear Collection and Glucose Measurement
Authors: Lee Seung Ho , Cho Yong Chan , Bin Choy Young
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
High-resolution polymer high performance liquid chromatography: optimization of the saw tooth gradient profile for various stationary phases and separations on preparative scale
Authors: Durner Bernhard , Ehmann Thomas , Matysik Frank-Michael
Published: September 2019

The recently introduced saw tooth gradient protocol for high-resolution polymer HPLC was further improved and optimized in terms of total runtime and separation performance.
The extraction of pyrethroid insecticides in juice and tea beverages by liquid-phase microextraction using deep eutectic solvents
Authors: Qian Heng , Liu Chaoran , Yang Qian , Liu Xinya , Gao Haixiang , Zhou Wenfeng
Published: September 2019

Deep eutectic solvents (DESs), a mixture of hydrogen bond acceptor and hydrogen bond donor compounds, were dispersed in a porous ceramic film for the determination of pyrethroid pesticides in juice and tea beverage samples using liquid-phase microextraction.
Na2MnP2O7 polymorphs as efficient bifunctional catalysts for oxygen reduction and oxygen evolution reactions
Authors: Gond Ritambhara , Vanam Sai Pranav , Barpanda Prabeer
Published: September 2019

Two polymorphs of pyrophosphate Na2MnP2O7 (P1̄ NMPy and P1 NMPy) were prepared by solid-state synthesis. Both polymorphs exhibited promising oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) electrocatalytic activities.
C–H and N–H bond annulation of aryl amides with unactivated olefins by merging cobalt(iii) and photoredox catalysis
Authors: Kalsi Deepti , Barsu Nagaraju , Chakrabarti Sagnik , Dahiya Pardeep , Rueping Magnus , Sundararaju Basker
Published: September 2019

A mild, environment-friendly protocol has been developed to carry out the [4+2] annulation of aryl amides with unactivated olefins.
Incorporation of γ-butyrolactone (GBL) dramatically lowers the phase transition temperature of formamidinium-based metal halide perovskites
Authors: Ruan Shuai , Fan Rong , Pai Narendra , Lu Jianfeng , Webster Nathan A. S. , Ruan Yinlan , Cheng Yi-Bing , McNeill Christopher R.
Published: September 2019

The phase transition temperature of formamidinium-based perovskites can be dramatically reduced through the incorporation of γ-butyrolactone (GBL).
Decamethylcucurbit[5]uril based supramolecular assemblies as efficient electrocatalysts for the oxygen reduction reaction
Authors: Chen Ruru , Cao Minna , Wang Jinyun , Li Hongfang , Cao Rong
Published: September 2019

A series of decamethylcucurbit[5]uril based supramolecular assemblies were successfully synthesized and explored as efficient electrocatalysts towards the oxygen reduction reaction.
Thermodynamics of the S2-to-S3 state transition of the oxygen-evolving complex of photosystem II
Authors: Amin Muhamed , Kaur Divya , Yang Ke R. , Wang Jimin , Mohamed Zainab , Brudvig Gary W. , Gunner M. R. , Batista Victor
Published: September 2019

The S2 to S3 transition in the OEC of PSII changes the structure of the Mn cluster. Monte Carlo sampling finds a Ca terminal water moves to form a bridge to Mn4 and the Mn1 ligand E189 can be replaced with a hydroxyl as a proton is lost.
Recent progress in Pt and Pd-based hybrid nanocatalysts for methanol electrooxidation
Authors: Shang Changshuai , Wang Erkang
Published: September 2019

Hybrid nanomaterials can combine merits of different components and modulate electronic states of Pt and Pd based nanocrystals simultaneously.
Tetranuclear oxido-bridged thorium(iv) clusters obtained using tridentate Schiff bases
Authors: Tsantis Sokratis T. , Lagou-Rekka Aimilia , Konidaris Konstantis F. , Raptopoulou Catherine P. , Bekiari Vlasoula , Psycharis Vassilis , Perlepes Spyros P.
Published: September 2019

The reactions of tetravalent thorium, an element named after the Scandinavian God of thunder and war, with tridentate Schiff bases give tetranuclear complexes with the extremely rare {ThIV4(μ4-O)} unit and interesting properties.