bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerability, pharmacokinetics, and pharmacodynamics of mirogabalin in healthy subjects: Results from phase 1 studies
Authors: Brown Karen , Mendell Jeanne , Ohwada Shoichi , Hsu Ching , He Ling , Warren Vance , Dishy Victor , Zahir Hamim
Published: August 2018

Three phase 1 pharmacokinetic (PK)/pharmacodynamics (PD) studies were conducted in healthy men and women to further characterize the safety, tolerability, andPK/PDof mirogabalin administration with or without food and to guide the dose selection and regimen for phase 2 and 3 clinical development. The 3 studies included 2 randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending‐dose studies, and 1 open‐label, crossover study to evaluate thePKof mirogabalin administered under fasting and fed (high‐fat meal) conditions. Forty‐eight and 47 healthy volunteers completed the single‐ and multiple‐dose studies, respectively. Thirty subjects were enrolled and completed the food effect study. Mirogabalin was well tolerated in the fed and fasted states. The most frequent treatment‐emergent adverse events (TEAEs)—dizziness and somnolence—were expected based on mirogabalin's mechanism of action. Subjects receiving the highest mirogabalin doses (50 and 75 mg single dose) showed greater dizziness and sedation and higher rates ofTEAEs than subjects receiving 3‐30 mg. After oral administration, mirogabalin was rapidly absorbed (time to maximum concentration, ∼1 hour) and eliminated through urine unchanged (61%‐72% urinary excretion). Exposure increased in a dose‐proportional manner after single or multiple mirogabalin doses. No significant accumulation occurred with multiple doses over 14 days. After single doses of mirogabalin (15 mg), the bioavailability was considered equivalent in the fed and fasted states, indicating that mirogabalin can be taken without food restrictions. Based on these data, mirogabalin 15 mg twice daily was selected as the highest target dose for further clinical development.
Small‐Molecule Neuromedin U Receptor 2 Agonists Suppress Food Intake and Decrease Visceral Fat in Animal Models
Authors: Sampson Catherine M. , Kasper James M. , Felsing Daniel E. , Raval Sweta R. , Ye Na , Wang Pingyuan , Patrikeev Igor , Rytting Erik , Zhou Jia , Allen John A. , Hommel Jonathan D.
Published: August 2018

Obesity is a growing public health concern, with 37.5% of the adult population in need of therapeutics that are more efficacious with a better side effect profile. An innovative target in this regard is neuromedin U, a neuropeptide shown to suppress food intake and attenuate weight gain in animal models. These effects of neuromedin U on feeding behavior are thought to be related to agonism at the centrally expressed neuromedin U receptor 2 (NMUR2). As peptides present unique challenges that limit their therapeutic potential, the discovery of small‐molecule NMUR2 agonists is needed to validate the targets therapeutic value, but to date, none have been evaluated in any animal model of disease. We therefore assessed two small‐molecule NMUR2 agonists for their in vitro signaling and their in vivo efficacy. The NMUR2 agonists were synthesized and both NMUR2 agonists, NY0116 and NY0128, decreased cAMP while stimulating calcium signaling in stably expressing NMUR2 HEK293 cells. When small‐molecule NMUR2 agonists were tested in vivo, acute administration significantly decreased high‐fat diet consumption. Repeated administration of the compounds decreased body weight and more specifically, decreased the percentage of visceral adipose tissue (VAT) in obese mice. These results have confirmed small‐molecule NMUR2 agonists are efficacious in animal models to decrease fat content, food intake, and body weight, suggesting NMUR2 is a promising therapeutic target for metabolic disorders.
Host plant influences establishment and performance of Amblydromalus limonicus, a predator for Bactericera cockerelli
Authors: Kean Aliesha M , Nielsen Mette‐Cecilie , Davidson Melanie M , Butler Ruth C , Vereijssen Jessica
Published: August 2018

BACKGROUND

Management of tomato potato psyllid (TPP; Bactericera cockerelli (Šulc)) predominantly relies on insecticides. However, biological control agents (BCAs) could provide viable alternatives to suppress TPP populations. In this laboratory experiment, we assessed the predatory mite Amblydromalus limonicus (Garman & McGregor) as a BCA of TPP on whole plants of two tomato and two pepper cultivars over a 5‐week period.

RESULTS

Plant species and cultivar had a significant effect on the ability of A. limonicus to suppress populations of TPP. Numbers of TPP were suppressed by A. limonicus on four pepper treatments, but on only one tomato treatment. Amblydromalus limonicus could survive and reproduce on pepper and tomato, but more were found on pepper at the end of the 5‐week period.

CONCLUSION

Amblydromalus limonicus has the potential to suppress TPP populations on pepper but not tomato cultivars, based on the present study. Possible reasons for these results include the difference in leaf morphology between species, and higher predator:prey ratios on pepper than tomato because of the longer TPP generation time on pepper. © 2018 Society of Chemical Industry
Systemic resistance inducer acibenzolar‐S‐methyl (ASM) and its microencapsulated formulations: their long‐lasting control efficacy against cucumber diseases and mitigation of phytotoxicity
Authors: Ishii Hideo , Fujiwara Masahiro , Nishimura Kumiko
Published: August 2018

BACKGROUND

The development of fungicide resistance by pathogens is a major limiting factor for the control of plant diseases. To combat resistance development, the use of broad‐spectrum but nonfungitoxic resistance inducers such as acibenzolar‐S‐methyl (ASM) is a promising approach because the orchestrated mechanisms underlying systemic acquired resistance induced by ASM are less likely to be overcome easily by pathogens. However, phytotoxicity is the main limiting factor of ASM.

RESULTS

ASM was highly active at inducing systemic resistance against powdery and downy mildews, the two major cucumber diseases. Based on the duration of the control, ASM effectiveness against these diseases was maintained well in plastic greenhouses and the number of sprays could be reduced. Control efficacy after seed treatment with ASM and the applications of microencapsulated ASM was also high against mildews in pots as well as in greenhouse experiments, with no problematic phytotoxicity.

CONCLUSION

The use of ASM is a potential integrated pest management‐based tactic to control cucumber powdery and downy mildews because its long‐lasting efficacy allows the application of typical fungicides to be reduced. The risk for resistance development in mildew pathogens will also be reduced. ASM seed treatment as well as soil amendment with microencapsulated ASM is effective in lowering the risk for the phytotoxicity of this compound. © 2018 Society of Chemical Industry
Attractiveness of host banana leaf materials to the banana weevil,Cosmopolites sordidusin Ghana for development of field management strategies
Authors: Abagale Samson A , Woodcock Christine M , Chamberlain Keith , Osafo‐Acquaah Samuel , van Emden Helmut , Birkett Michael A , Pickett John A , Braimah Haruna
Published: August 2018

BACKGROUND

The banana weevil,Cosmopolites sordidus, has been frequently cited as the most challenging constraint to banana and plantain production, particularly in small‐scale (smallholder) farming. For the development of a new, low‐cost weevil management technology based on attractive host plant material, we previously identified (2R,5S)‐theaspirane as the active component of attractive senesced banana leaves. In this new study, we used behavioural (olfactometer) bioassays with adult weevils to compare the attractiveness of four different developmental stages of banana leaves, i.e. unfolding (pale green), matured green (deep green), matured yellowing and senesced, to determine which leaf developmental stage would be most appropriate for use in weevil management. We also investigated the attractiveness of senesced leaf extracts prepared using different solvents to determine which solvent would be most appropriate for local production of leaf extracts. Coupled gas chromatography–electroantennography (GC–EAG) was then used with adult weevils to confirm the presence of (2R,5S)‐theaspirane in attractive leaf extracts.

RESULTS

Of the leaf materials tested, only the odour of senesced leaf material was significantly attractive to adult weevils (P < 0.005). Furthermore, an extract of senesced material prepared using palm wine alcohol was significantly attractive (P < 0.05). Using coupled GC–EAG with weevil antennae, (2R,5S)‐theaspirane was identified as a minor component with strong EAG activity within the palm wine alcohol extract.

CONCLUSION

The results suggest that palm wine alcohol extracts of senesced banana leaf material could be used to lure adultC. sordidusto traps in the field, as part of an ethnobotanical‐based approach forC. sordidusmanagement on smallholder farms. © 2018 The Authors.Pest Management Sciencepublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
An Efficient, Scalable Route to Robust PVDF‐co‐HFP/SiO2 Separator for Long‐Cycle Lithium Ion Batteries
Authors: Boateng Bismark , Zhu Gaolong , Lv Weiqiang , Chen Dongjiang , Feng Chao , Waqas Muhammad , Ali Shamshad , Wen Kechun , He Weidong
Published: August 2018

A highly uniform, heterogeneous‐phase composite separator is synthesized by a direct post‐solidation process from the mixture of nano‐SiO2/acetone monodisperse suspension and poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐co‐HFP)/acetone gel, without any organic surfactants. This technique leads to the PVDF‐co‐HFP/SiO2 composite separator outstanding microstructural uniformity. The incorporation of SiO2 nanoparticles leads to reduced crystallinity (≈27%), enhanced wettability (≈14%), improved electrolyte uptake (≈420%), and enhanced mechanical strength (>14 MPa) of the composite separator. These enhanced properties of the separator translate into remarkable LiFePO4/Li battery performance with reduced polarization, a high room‐temperature capacity of 165 mAh g−1 at 0.5 C, a high thermal dimensional stability (≈4.5% shrinkage after annealing at 160 °C for 1 h) and 5.2% capacity degradation after 1500 charge/discharge cycles at 2 C.
Reversal and momentum patterns in weekly stock returns: European evidence
Authors: Hühn Hannah Lea , Scholz Hendrik
Published: August 2018

We analyze short‐term reversal and medium‐term momentum patterns in weekly stock returns in Europe. Focusing on raw and stock‐specific returns, our empirical results show for both return specifications (a) a negative relation between weekly past returns and future returns in the short run and (b) a positive relation in the medium run. However, returns from reversal and momentum strategies based on stock‐specific returns are less volatile. In further analyses, we find short‐term reversal and medium‐term momentum patterns to be connected to stock characteristics. Looking at the potential causes of these effects, our results do not support the idea that short‐term reversal in weekly stock returns is due to an over‐ or underreaction to firm‐specific news nor that it is mainly driven by illiquidity. Medium‐term momentum in weekly stock returns, on the other hand, can be connected to behavioral biases. Our concluding tests confirm that our findings are robust among industries, in subperiods, for the January effect and in varying market states. Finally, while medium‐term momentum strategies remain profitable after accounting for transaction costs, short‐term reversal strategies can be mainly explained by transaction costs due to their high turnover.
Semi‐global leader‐following output consensus of heterogeneous multi‐agent systems with input saturation
Authors: Shi Liangren , Li Yuanlong , Lin Zongli
Published: August 2018

In this paper, we consider the semi‐global leader‐following output consensus problem for a heterogeneous multi‐agent system with input saturation over a directed network on which the leader agent is globally reachable. By using the low gain feedback technique and the output regulation theory, we construct two consensus protocols, of the state feedback type and the output feedback type. In the state feedback case, a distributed leader state observer is constructed to estimate the leader state for each follower agent. In the output feedback case, follower agents are divided into two groups, namely, the informed follower agents that have access to the information of the leader agent and the uninformed follower agents that have not. Besides a distributed leader state observer that is designed for the uninformed agents, state observers are constructed for each follower agents. Based on these observers, the consensus protocols can solve the semi‐global leader‐following output consensus problem. Simulation results illustrate the effectiveness of our proposed approaches.
H∞ mixed stabilization of nonlinear parameter‐varying systems
Authors: Fu Rong , Zeng Jianping , Duan Zhisheng
Published: August 2018

This paper generalizes the existing finite‐time stability (FTS) analysis/synthesis research to nonlinear time‐varying systems in the nonlinear parameter‐varying (NPV) framework. Specifically, to guarantee both the transient and steady‐state performances for NPV systems with external disturbance and input constraints, concepts of mixed stability and mixed stability with H∞ disturbance attenuation are proposed, together with the corresponding analysis and synthesis methods. Differently from the existing FTS‐related works, the mixed stability in this paper consists of properties of uniform exponential stability in addition to FTS. Existence conditions for an nonlinear time‐varying controller to render an NPV system mixed stable with H∞ disturbance attenuation are given in terms of state‐and‐parameter–dependent linear matrix inequalities. The generalized S‐procedure is used to convexify the input constraints such that the resulting closed‐loop system satisfies the input constraints for any state starting from an admissible set. For the case that both parameters and state are subject to restricted regions, local synthesis results are also provided. All the conditions are in the form of state‐and‐parameter–dependent linear matrix inequalities, which can be efficiently solved by using sum‐of‐squares programming. A simulation example validates the effectiveness of the proposed approach.
Impact of Soaking Time at Room Temperature on the Physicochemical Properties of Maize and Potato Starch Granules
Authors: Alvarez‐Ramírez José , Vernon‐Carter Eduardo Jaime , Carrillo‐Navas Hector , Meraz Monica
Published: August 2018

Starch‐rich foods such as cereals and tubers are the main source of energy in human diet, but are rarely consumed in their native form, requiring cooking to deem them more digestible. The soaking of starch‐rich matrices can reduce significantly energy consumption. In this work, native maize and potato starches are soaked in water (10 g/100 g water) at room temperature (20 °C) for up to 8 h, and the physicochemical changes (morphology, particle size, apparent viscosity, and crystallinity changes) are monitored for soaking times of 1, 2, 4, 6, and 8 h. Starch granules lose gradually birefringence, while the mean particle size increases by 7.0–9.0% by swelling effect. The apparent viscosity of the starch dispersion also increases about 5–7 times after 8 h of soaking. Differential scanning calorimetry shows that the enthalpy required for achieving complete gelatinization decreased by about 80–90% after the 8 h soaking treatment. Overall, the results indicated that soaking at room temperature offers an inexpensive mean for saving energy cost involved in starch gelatinization process.
Chinese venture investments in the United States, 2010–2017
Authors: Gonzales John , Ohara Frank
Published: August 2018

This article contributes to the understanding of Chinese venture investors in the United States by comprehensively measuring the amount and type of venture investments coming to the United States from China. Venture activity is examined by focusing on the number of investments made by venture capital funds, both U.S.‐ and China‐based that include Chinese corporations undertaking corporate venture capital (CVC). Chinese participation in venture funding of United States emerging companies increased from 21 investments in 2010 to 407 in 2016 and 2017. Venture capital funds account for 78% of the investment activity, with Chinese CVC undertaking 22% of the investments. We contribute to the literature of CVC by providing definitions of three specific types of investing firms: corporate funds, strategic investors, and strategic partnerships. In addition, we provide data and examine the motivations of Chinese firms forming strategic partnerships with United States startups.
Treatment of twin‐reversed arterial perfusion sequence using high‐intensity focused ultrasound
Authors: Seo K. , Ichizuka K. , Okai T. , Dohi S. , Nakamura M. , Hasegawa J. , Matsuoka R. , Yoshizawa S. , Umemura S.‐I. , Nagatsuka M. , Sekizawa A.
Published: August 2018

We describe our experience of high‐intensity focused ultrasound (HIFU) for fetal therapy in twin‐reversed arterial perfusion (TRAP) sequence. Six pregnant women underwent HIFU therapy, five before 16 weeks and one at 26 weeks. Two types of HIFU system were used: the first‐generation system, which comprised a biaxial transducer and continuous exposure pattern, and the second‐generation system, which comprised a coaxial transducer and sequential exposure pattern. The first‐generation apparatus was used in four cases and the second‐generation apparatus was used in two. In three cases, occlusion of the blood vessels mediating flow to the acardiac twin was achieved by HIFU. Two cases experienced intrauterine fetal death despite vessel occlusion. The total survival rate of pump fetuses 2 years after HIFU was 67% and the efficiency rate (the proportion of cases with occlusion or reduced blood flow on ultrasound after HIFU) was 83%. After more than 2 years of follow‐up, the surviving infants had no severe clinical complications and no postnatal developmental problems. There was no significant difference in survival rate compared with TRAP cases managed expectantly. Given that complete occlusion of the blood vessels was not achieved in half of the cases, we could not show that HIFU therapy is superior to other treatments. However, HIFU can reduce the cardiac load of the pump fetus and, as it does not require uterine puncture for fetal therapy, there were no fatal complications, such as bleeding, rupture of membranes or infection. Thus, HIFU therapy may represent a less‐invasive treatment for TRAP sequence in early pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Interferometric Water Level Tilt Meter Development in Finland and Comparison with Combined Earth Tide and Ocean Loading Models
Authors: Ruotsalainen Hannu
Published: August 2018

A modern third-generation interferometric water level tilt meter was developed at the Finnish Geodetic Institute in 2000. The tilt meter has absolute scale and can do high-precision tilt measurements on earth tides, ocean tide loading and atmospheric loading. Additionally, it can be applied in various kinds of geodynamic and geophysical research. The principles and results of the historical 100-year-old Michelson–Gale tilt meter, as well as the development of interferometric water tube tilt meters of the Finnish Geodetic Institute, Finland, are reviewed. Modern Earth tide model tilt combined with Schwiderski ocean tide loading model explains the uncertainty in historical tilt observations by Michelson and Gale. Earth tide tilt observations in Lohja2 geodynamic station, southern Finland, are compared with the combined model earth tide and four ocean tide loading models. The observed diurnal and semidiurnal harmonic constituents do not fit well with combined models. The reason could be a result of the improper harmonic modelling of the Baltic Sea tides in those models.
Measuring the ratio of HW W and HZZ couplings through W +W −H production
Authors: Chiang Cheng-Wei , He Xiao-Gang , Li Gang
Published: August 2018

Abstract

For a generic Higgs boson, measuring the relative sign and magnitude of its couplings with the W and Z bosons is essential in determining its origin. Such a test is also indispensable for the 125-GeV Higgs boson. We propose that the ratio of the HW W and HZZ couplings λ

W Z
can be directly determined through the W
+
W
−
H production, where H denotes a generic Higgs boson, owing to the tree-level interference effect. While this is impractical at the LHC due to the limited sensitivity, it can be done at future e
+
e
− colliders, such as a 500-GeV ILC with the beam polarization P (e
−
, e
+) = (−0.8, +0.3) in the jjℓ
±
bb and ℓ
±
ℓ
±
ℓ
∓
jj channels. The discovery potential of a general ratio and the power to discriminate it from the SM value are studied in detail. Combining the cross section of e
+
e
− → W
+
W
−
H with the measurements of HZZ coupling at the HL-LHC, one can further improve the sensitivity of λ

W Z
.
Einstein-AdS action, renormalized volume/area and holographic Rényi entropies
Authors: Anastasiou Giorgos , Araya Ignacio J. , Arias Cesar , Olea Rodrigo
Published: August 2018

Abstract

We exhibit the equivalence between the renormalized volume of asymptotically anti-de Sitter (AAdS) Einstein manifolds in four and six dimensions, and their renormalized Euclidean bulk gravity actions. The action is that of Einstein gravity, where the renormalization is achieved through the addition of a single topological term. We generalize this equivalence, proposing an explicit form for the renormalized volume of higher even-dimensional AAdS Einstein manifolds. We also show that evaluating the renormalized bulk gravity action on the conically singular manifold of the replica trick results in an action principle that corresponds to the renormalized volume of the regular part of the bulk, plus the renormalized area of a codimension-2 cosmic brane whose tension is related to the replica index. Renormalized Rényi entropy of odd-dimensional holographic CFTs can thus be obtained from the renormalized area of the brane with finite tension, including the effects of its backreaction on the bulk geometry. The area computation corresponds to an extremization problem for an enclosing surface that extends to the AdS boundary, where the newly defined renormalized volume is considered.
Quantum teleportation through time-shifted AdS wormholes
Authors: van Breukelen Rik , Papadodimas Kyriakos
Published: August 2018

Abstract

Based on the work of Gao-Jafferis-Wall and Maldacena-Stanford-Yang, we observe that the time-shifted thermofield states of two entangled CFTs can be made traversable by an appropriate coupling of the two CFTs, or alternatively by the application of a modified quantum teleportation protocol. This provides evidence for the smoothness of the horizon for a large class of entangled states related to the thermofield by time-translations. The smoothness of these states has some relevance for the firewall paradox and the proposal that some observables in quantum gravity may be state-dependent. We notice that quantum teleportation through these entangled states could be used in a laboratory setup to implement a “time-machine”, which allows the observer to travel far in the future.
Quantum complexity and the virial theorem
Authors: Bao Ning , Liu Junyu
Published: August 2018

Abstract

It is conjectured that in the geometric formulation of quantum computing, one can study quantum complexity through classical entropy of statistical ensembles established non-relativistically in the group manifold of unitary operators. The kinetic and positional decompositions of statistical entropy are conjectured to correspond to the Kolmogorov complexity and computational complexity, respectively, of corresponding quantum circuits. In this paper, we claim that by applying the virial theorem to the group manifold, one can derive a generic relation between Kolmogorov complexity and computational complexity in the thermal equilibrium.
More than Moore’s Mores: Computers, Genomics, and the Embrace of Innovation
Authors: November Joseph
Published: August 2018

The genomics community has frequently compared advances in sequencing to advances in microelectronics. Lately there have been many claims, including by the National Human Genome Research Institute (NHGRI), that genomics is outpacing developments in computing as measured by Moore's law – the notion that computers double in processing capability per dollar spent every 18-24 months. Celebrations of the “$1000 genome” and other speed-related sequencing milestones might be dismissed as a distraction from genomics' slowness in delivering clinical breakthroughs, but the fact that such celebrations have been persistently encouraged by the NHGRI reveals a great deal about the priorities and expectations of the American general public, the intended audience of the genomics–computing comparison. By delving into the history of speculative thinking about sequencing and computing, this article demonstrates just how much more receptive to high-risk/high-payoff ventures the NIH and the general public have become. The article also provides access to some of the roots and consequences of the association of “innovation talk” with genomics, and the means to look past that association to the less glamorous (but arguably much more important) contributions of the NHGRI to building the field of genomics.
The Favorable Effect of Empagliflozin on Erectile Function in an Experimental Model of Type 2 Diabetes
Authors: Assaly Rana , Gorny Diane , Compagnie Sandrine , Mayoux Eric , Bernabe Jacques , Alexandre Laurent , Giuliano François , Behr-Roussel Delphine
Published: August 2018

Introduction

Following the results of the EMPA-REG Outcome trial, we hypothesized that empagliflozin, a highly potent and specific sodium/glucose cotransporteur 2 inhibitor, could improve type 2 diabetes mellitus (T2DM)-associated erectile dysfunction (ED), a highly prevalent complication of T2DM, very often coexisting with cardiovascular complications and considered as a prognostic factor of cardiovascular disease in men with diabetes.

Aim

To investigate the effects of chronic treatment with empagliflozin on ED in a T2DM rat model in the presence or absence of sildenafil.

Methods

Male Goto-Kakizaki (GK), a model of T2DM, and age-matched Wistar rats received placebo or empagliflozin treatment at 25.3 ± 0.9 mg/kg/d for 4 weeks. Then, the in vivo effect of empagliflozin on erectile function was assessed by electrical stimulation of the cavernous nerve at different frequencies under anesthesia in the presence or absence of acute intravenous injection of sildenafil. Endothelium-dependent, -independent, and nitrergic relaxations of cavernosal strips from the rats were studied.

Main Outcome Measures

Body weight, food consumption, metabolic parameters, plasma inflammation biomarkers, and in vivo erectile responses elicited by electrical stimulation of the cavernous nerve in empagliflozin-treated and untreated GK rats and control Wistar rats were assessed and followed by concentration or frequency response curves to endothelium-dependent, -independent, and nitrergic relaxations of cavernosal strips from these rats.

Results

Chronic empagliflozin followed by acute sildenafil significantly improved erectile responses in adult GK rats (n = 12–15/group). Ratios of intracavernous pressure and area under the curve/mean arterial pressure during the electrical stimulation were significantly increased in empagliflozin-treated vs untreated GK rats. Nitrergic relaxations of cavernosal strips from GK rats were significantly increased with empagliflozin compared with placebo. Moreover, the effect of sildenafil on erectile function was not altered by empagliflozin treatment.

Clinical Implications

Empagliflozin may benefit T2DM patient with ED.

Strengths & Limitations

The mechanism(s) by which empagliflozin shows favorable effect on erectile function in GK rats needs to be further elucidated.

Conclusion

Empagliflozin shows favorable effect on erectile function in diabetic GK rats mediated by an improvement of nitrergic relaxation of erectile tissue. Whether this favorable effect on ED in the experimental context of T2DM is due to better glycemic control or to another effect of empagliflozin deserves further investigation.
Bacterial communities of cryoconite holes of a temperate alpine glacier show both seasonal trends and year-to-year variability
Authors: Pittino Francesca , Maglio Maurizio , Gandolfi Isabella , Azzoni Roberto Sergio , Diolaiuti Guglielmina , Ambrosini Roberto , Franzetti Andrea
Published: August 2018

Cryoconite holes are small depressions of the glacier surface filled with melting water and with a wind-blown debris on the bottom. These environments are considered hot spots of biodiversity and biological activities on glaciers and host communities dominated by bacteria. Most of the studies on cryoconite holes assume that their communities are stable. However, evidence of seasonal variation in cryoconite hole ecological communities exists. We investigated the variation of the bacterial communities of cryoconite holes of Forni Glacier (Central Italian Alps) during the melting seasons (July–September) 2013 and 2016, for which samples at three and five time-points, respectively were available. Bacterial communities were characterized by high-throughput Illumina sequencing of the hypervariable V5−V6 regions of 16S rRNA gene, while meteorological data were obtained by an automatic weather station. We found consistent trends in bacterial communities, which shifted from cyanobacteria-dominated communities in July to communities dominated by heterotrophic orders in late August and September. Temperature seems also to affect seasonal dynamics of communities. We also compared bacterial communities at the beginning of the melting season across 4 years (2012, 2013, 2015 and 2016) and found significant year-to-year variability. Cryoconite hole communities on temperate glaciers are therefore not temporally stable.
The linear instability of the stratified plane Couette flow
Authors: Facchini Giulio , Favier Benjamin , Le Gal Patrice , Wang Meng , Le Bars Michael
Published: August 2018

We present the stability analysis of a plane Couette flow which is stably stratified in the vertical direction orthogonal to the horizontal shear. Interest in such a flow comes from geophysical and astrophysical applications where background shear and vertical stable stratification commonly coexist. We perform the linear stability analysis of the flow in a domain which is periodic in the streamwise and vertical directions and confined in the cross-stream direction. The stability diagram is constructed as a function of the Reynolds number$Re$and the Froude number$Fr$, which compares the importance of shear and stratification. We find that the flow becomes unstable when shear and stratification are of the same order (i.e. $Fr\sim 1$) and above a moderate value of the Reynolds number$Re\gtrsim 700$. The instability results from a wave resonance mechanism already known in the context of channel flows – for instance, unstratified plane Couette flow in the shallow-water approximation. The result is confirmed by fully nonlinear direct numerical simulations and, to the best of our knowledge, constitutes the first evidence of linear instability in a vertically stratified plane Couette flow. We also report the study of a laboratory flow generated by a transparent belt entrained by two vertical cylinders and immersed in a tank filled with salty water, linearly stratified in density. We observe the emergence of a robust spatio-temporal pattern close to the threshold values of$Fr$and$Re$indicated by linear analysis, and explore the accessible part of the stability diagram. With the support of numerical simulations we conclude that the observed pattern is a signature of the same instability predicted by the linear theory, although slightly modified due to streamwise confinement.
Exit, Voice, and Public Reason
Authors: VALLIER KEVIN
Published: August 2018

Public reason liberals appeal to public deliberation to ensure that a legal order can be publicly justified to its citizens. I argue that thisvoicemechanism should be supplemented byexitmechanisms. By allowing citizens to exit legal orders they believe cannot be publicly justified, citizens can pressure states to change their laws. This exit pressure is sometimes more effective than deliberation. I explore federalism as an exit mechanism that can help public deliberation establish a publicly justified polity.
WHAT WE DON'T SEE WHEN WE SEE COPYRIGHT AS PROPERTY
Authors: Litman Jessica
Published: August 2018

For all of the rhetoric about the central place of authors in the copyright scheme, our copyright laws in fact give them little power and less money. Intermediaries own the copyrights, and are able to structure licenses so as to maximise their own revenue while shrinking their pay-outs to authors. Copyright scholars have tended to treat this point superficially, because – as lawyers – we take for granted that copyrights are property; property rights are freely alienable; and the grantee of a property right stands in the shoes of the original holder. I compare the 1710 Statute of Anne, which created statutory copyrights and consolidated them in the hands of publishers and printers, with the 1887 Dawes Act, which served a crucial function in the American divestment of Indian land. I draw from the stories of the two laws the same moral: Constituting something as a freely alienable property right will almost always lead to results mirroring or exacerbating disparities in wealth and bargaining power. The legal dogma surrounding property rights makes it easy for us not to notice.
EVIDENCE REQUIRED BY HEALTH TECHNOLOGY ASSESSMENT AND REIMBURSEMENT BODIES EVALUATING DIAGNOSTIC OR PROGNOSTIC ALGORITHMS THAT INCLUDE OMICS DATA
Authors: Barna Alexandre , Cruz-Sanchez Teresita M , Brigham Karen Berg , Thuong Cong-Tri , Kristensen Finn Boerlum , Durand-Zaleski Isabelle
Published: August 2018

Objectives:

Multi-analyte assays with algorithmic analyses (MAAAs) use combinations of circulating and clinical markers including omics-based sources for diagnostic and/or prognostic purposes. Assessing MAAAs is challenging under existing health technology assessment (HTA) methods or practices. We undertook a scoping review to explore the HTA methods used for MAAAs to identify the criteria used for clinical research and reimbursement purposes.

Methods:

This review included only non-companion (stand-alone) tests that are actionable and that have been evaluated by leading HTA or insurer/reimbursement bodies up to September 2017.

Results:

Twenty-five reports and articles evaluating seventeen MAAAs were examined, most of which have been developed in oncology. The two main models used were the EUnetHTA Core model and the Evaluation of Genomic Applications in Practice and Prevention ACCE framework. Clinical validity and utility criteria were used, as were economic, ethical, legal, and social aspects. Economic evidence on MAAAs was scarce, and there is no consensus on whether the perspectives used are sufficiently broad to include all relevant stakeholders.

Conclusions:

Clinical utility and efficiency were the most used criteria, with stronger evidence needed linking the use of the algorithm with the clinical outcomes in real-life practice. HTA bodies must as well consider questions related to the analytical validity of MAAAs or with organizational aspects. The two main models, the EUnetHTA Core model and the ACCE framework, could be adapted to the assessment of MAAAs.
February–May 2018
Authors: Cranmer Frank
Published: August 2018

On 23 March, the European Council agreed the terms of a Brexit transition period under which the United Kingdom's phased departure will last for 21 months, ending in December 2020. The European Union (Withdrawal) Bill completed its consideration in the House of Lords with Government defeats on several issues, perhaps the most controversial of which were amendments requiring the Government to explore the option of staying in a customs union (by a majority of 123), limiting the ability to use secondary legislation to change existing EU rights after they have been transposed into domestic law (by a majority of 97) and retaining most of the EU Charter of Fundamental Rights on the statute book after Brexit (by a majority of 71).
THE LOOMIS–SIKORSKI THEOREM FOR -ALGEBRAS
Authors: DVUREČENSKIJ ANATOLIJ , ZAHIRI OMID
Published: August 2018

An EMV-algebra resembles an MV-algebra in which a top element is not guaranteed. For$\unicode[STIX]{x1D70E}$-complete$EMV$-algebras, we prove an analogue of the Loomis–Sikorski theorem showing that every$\unicode[STIX]{x1D70E}$-complete$EMV$-algebra is a$\unicode[STIX]{x1D70E}$-homomorphic image of an$EMV$-tribe of fuzzy sets where all algebraic operations are defined by points. To prove it, some topological properties of the state-morphism space and the space of maximal ideals are established.
Magnetospheric Source Region of Auroral Finger‐like Structures Observed by the RBSP‐A Satellite
Authors: Nishi Katsuki , Shiokawa Kazuo , Spence Harlan
Published: August 2018

Auroral finger‐like structures appear equatorward of the auroral oval in the diffuse auroral region and contribute to the auroral fragmentation into patches. A previous report of the first conjugate observation of auroral finger‐like structures using a Time History of Events and Macroscale Interactions during Substorms (THEMIS) Ground‐Based Observatories camera and the THEMIS‐E satellite at a radial distance of ∼8 RE showed antiphase oscillations of magnetic and plasma pressures in the dawnside plasma sheet. In the present study, we report another simultaneous observation of auroral finger‐like structures at Gillam, Canada, at ∼0900 UT (0230 magnetic local time) on 14 November 2014 with the Radiation Belt Storm Probes satellites at 5.8 RE in the inner magnetosphere. From this simultaneous observation event, we obtained the following observations. (1) Auroral finger‐like structures developed poleward in the equatorward moving auroral arc at the equatorward edge of the auroral oval. (2) Both the electron and ion OMNI fluxes measured by HOPE increased at ∼0900 UT as the satellite footprint entered the auroral region, indicating that the satellite was crossing the observed auroral finger‐like structures. (3) The absolute value of magnetic pressure was several times that of the plasma pressure, and no systematic phase relationship was identified between the magnetic and plasma pressures, unlike that in the THEMIS case. Based on these observations, we discuss two possible causes of the observed finger‐like structures, namely, pressure‐driven instability in the magnetosphere and gradient drift instability in the ionosphere. In this paper, the latter possibility is newly suggested to develop in the equatorward moving aurora associated with the westward electric field in the equatorward ionospheric density gradient.
Evolution and Distribution of the Early Aftershocks Following the 2008 Mw 7.9 Wenchuan Earthquake in Sichuan, China
Authors: Yin Xin Zhong , Chen Jiu Hui , Peng Zhigang , Meng Xiaofeng , Liu Qi Yuan , Guo Biao , Li Shun Cheng
Published: August 2018

Using seismic data recorded by a dense temporary seismic array, we apply a waveform matched‐filter technique and obtain an early aftershock catalog around the mainshock rupture zone of the 2008 Wenchuan, Sichuan, China, earthquake. Specifically, we use 1,273 events in a relocated aftershock catalog as templates and scan through the waveforms within 7 days following the mainshock. We obtain up to ∼5.3 and ∼10 times more aftershocks than the standard and relocated catalogs, respectively. We find that early aftershocks mostly occurred below 10 km depth, downdip to large coseismic slip areas. Early aftershocks also show minor along‐strike migration with time since the mainshock, indicating triggering of afterslip following the mainshock. From the epicentral region to Beichuan where the mainshock slip was primarily reverse faulting, early aftershocks illustrated the Yingxiu‐Beichuan and Guanxian‐Jiangyou faults as high‐angle listric feature and rooted to a gentle dipping plane at the depth of ∼20 km. The aftershocks in the northeast segment of the Longmen Shan faults mostly occurred along a near‐vertical dipping fault, consistent with the primary strike‐slip component of mainshock slip in this region. In addition, differences in early and long‐term aftershock distribution indicate significant postseismic deformation along the conjugate Xiaoyudong fault. Our results help to illuminate the deep geometry of the Longmen Shan fault zone and the early evolution after the Wenchuan mainshock, which provides additional constraints to the mechanism of plateau uplifting.
Reassessing the Thermal Structure of Oceanic Lithosphere With Revised Global Inventories of Basement Depths and Heat Flow Measurements
Authors: Richards F. D. , Hoggard M. J. , Cowton L. R. , White N. J.
Published: August 2018

Half‐space cooling and plate models of varying complexity have been proposed to account for changes in basement depth and heat flow as a function of lithospheric age in the oceanic realm. Here, we revisit this well‐known problem by exploiting a revised and augmented database of 2,028 measurements of depth to oceanic basement, corrected for sedimentary loading and variable crustal thickness, and 3,597 corrected heat flow measurements. Joint inverse modeling of both databases shows that the half‐space cooling model yields a mid‐oceanic axial temperature that is >100°C hotter than permitted by petrologic constraints. It also fails to produce the observed flattening at old ages. Then, we investigate a suite of increasingly complex plate models and conclude that the optimal model requires incorporation of experimentally determined temperature‐ and pressure‐dependent conductivity, expansivity, and specific heat capacity, as well as a low‐conductivity crustal layer. This revised model has a mantle potential temperature of 1300 ± 50°C, which honors independent geochemical constraints and has an initial ridge depth of 2.6 ± 0.3 km with a plate thickness of 135 ± 30 km. It predicts that the maximum depth of intraplate earthquakes is bounded by the 700°C isothermal contour, consistent with laboratory creep experiments on olivine aggregates. Estimates of the lithosphere‐asthenosphere boundary derived from studies of azimuthal anisotropy coincide with the 1175 ± 50°C isotherm. The model can be used to isolate residual depth and gravity anomalies generated by flexural and sub‐plate convective processes.
Revisiting the Paleomagnetic Reversal Test: A Bayesian Hypothesis Testing Framework for a Common Mean Direction
Authors: Heslop D. , Roberts A. P.
Published: August 2018

For over 60 years a suite of field tests has provided paleomagnetists with a means to evaluate the timing of magnetic remanence acquisition and subsequent remanence stability. These tests are crucial for detecting potential overprinting by secondary remanences and for assessing the fidelity of the geological information carried by paleomagnetic signals. The reversal test was developed to detect secondary remanent magnetizations that could potentially bias paleomagnetic reconstructions. More recently, the reversal test has been applied to a broader set of problems, which require statistical assessment of common or antipodal paleomagnetic directions. From a statistical standpoint, the reversal test must distinguish whether two sets of paleomagnetic directions originate from populations with a common mean. However, earlier work has demonstrated that the reversal test may be ambiguous for small numbers of observations because insufficient information is available to reject the null hypothesis of a common mean direction. Here we develop a Bayesian framework to estimate directly the probability that two Fisher‐distributed sets of directions originate from populations with a common mean. This framework can be used to consider data sets with common or different precisions and, thus, provides a fully probabilistic version of the parametric reversal test. Additionally, adoption of a Bayesian framework means that ambiguity associated with the lack of information provided by small numbers of observations is incorporated into the final probability estimate in a natural way. Our new Bayesian test is demonstrated with numerical examples and case studies.
Seaglider Surveys at Ocean Station Papa: Oxygen Kinematics and Upper‐Ocean Metabolism
Authors: Pelland Noel A. , Eriksen Charles C. , Emerson Steven R. , Cronin Meghan F.
Published: August 2018

Understanding variability in annual net community production (NCP) and factors affecting its estimation are important priorities for the study of ocean biogeochemistry. The time evolution of dissolved oxygen is useful proxy for NCP if the physical tendency can be isolated and removed; a key challenge is the resolution of the terms contributing to this tendency. Here oxygen balances are examined in the upper 200 m at Ocean Station Papa (50°N, 145°W) using data from Seaglider surveys June 2008 to January 2010. Sampling of horizontal gradients of oxygen, temperature, and salinity during these surveys allows the inference of monthly three‐dimensional advection and turbulent diffusion of oxygen. The resulting monthly oxygen balances show strong variability with depth, with similarities to the temperature balances shallower than 100 m and salinity balances deeper. The estimated annual NCP of 2.2 ± 1.2 mol C·m−2·year−1 in the top 120 m is in agreement with contemporary studies in the subarctic North Pacific Ocean. Horizontal advection in the surface layer is found to be small as previously assumed but important at greater depths: Assuming zero horizontal advection in the top 120 m would have resulted in an overestimate of annual NCP by 50%. Horizontal and vertical advection together dominated the oxygen balance in the permanent pycnocline. Results emphasize the three‐dimensional nature of the oxygen balance, even in this relatively quiescent location, and further demonstrate the viability of autonomous spatial surveys for resolving physical oxygen transport terms.
An imputation platform to enhance integration of rice genetic resources
Authors: Wang Diane R. , Agosto-Pérez Francisco J. , Chebotarov Dmytro , Shi Yuxin , Marchini Jonathan , Fitzgerald Melissa , McNally Kenneth L. , Alexandrov Nickolai , McCouch Susan R.
Published: August 2018

As sequencing and genotyping technologies evolve, crop genetics researchers accumulate increasing numbers of genomic data sets from various genotyping platforms on different germplasm panels. Imputation is an effective approach to increase marker density of existing data sets toward the goal of integrating resources for downstream applications. While a number of imputation software packages are available, the limitations to utilization for the rice community include high computational demand and lack of a reference panel. To address these challenges, we develop the Rice Imputation Server, a publicly available web application leveraging genetic information from a globally diverse rice reference panel assembled here. This resource allows researchers to benefit from increased marker density without needing to perform imputation on their own machines. We demonstrate improvements that imputed data provide to rice genome-wide association (GWA) results of grain amylose content and show that the major functional nucleotide polymorphism is tagged only in the imputed data set.