bluuebunny/crossref_metadata_2025 huggingface dataset:
How Reliable is Duality Theory in Empirical Work?
Authors: Rosas Francisco , Lence Sergio H.
Published: September 2018

The Neoclassical theory of production establishes a dual relationship between the profit value function of a competitive firm and its underlying production technology. This relationship, commonly referred to as duality theory, has been widely used in empirical work to estimate production parameters such as elasticities and returns to scale. We generate a pseudo‐dataset by Monte Carlo simulations, which, starting from known production parameters, yield a dataset with the main characteristics of U.S. agriculture in terms of unobserved firm heterogeneity, decisions under uncertainty, unexpected production and price shocks, endogenous prices, output and input aggregation, measurement error in variables, and omitted variables. Production parameters are not precisely recovered when performing econometric estimation based on the duality approach, and the elasticity estimates are inaccurate. Deviations of own‐ and cross‐price elasticities from initial median values, given our parameter calibration, range between 6% and 690%, with an average of 90%. Also, own‐price elasticities are as imprecisely recovered as cross‐price elasticities. Sensitivity analysis shows that results still hold for different sources and levels of noise, and sample size used in estimation.
An omega-3 polyunsaturated fatty acid derivative, 18-HEPE, protects against CXCR4-associated melanoma metastasis
Authors: Li Jieping , Chen Chih-Yu , Arita Makoto , Kim Kuijin , Li Xiangyong , Zhang Hongman , Kang Jing X
Published: September 2018

Melanoma has a high propensity to metastasize and exhibits a poor response to classical therapies. Dysregulation of the chemokine receptor gene CXCR4 is associated with melanoma progression, and although n-3 polyunsaturated fatty acids (PUFAs) are known to be beneficial for melanoma prevention, the underlying mechanism of this effect is unclear. Here, we used the n-3 fatty acid desaturase (Fat-1) transgenic mouse model of endogenous n-3 PUFA synthesis to investigate the influence of elevated n-3 PUFA levels in a mouse model of metastatic melanoma. We found that relative to wild-type (WT) mice, Fat-1 mice exhibited fewer pulmonary metastatic colonies and improved inflammatory indices, including reduced serum tumor necrosis factor alpha (TNF-α) levels and pulmonary myeloperoxidase activity. Differential PUFA metabolites in serum were considered a key factor to alter cancer cell travelling to lung, and we found that n-6 PUFAs such as arachidonic acid induced CXCR4 protein expression although n-3 PUFAs such as eicosapentaenoic acid (EPA) decreased CXCR4 levels. In addition, serum levels of the bioactive EPA metabolite, 18-HEPE, were elevated in Fat-1 mice relative to WT mice, and 18-HEPE suppressed CXCR4 expression in B16-F0 cells. Moreover, relative to controls, numbers of pulmonary metastatic colonies were reduced in WT mice receiving intravenous injections either of 18-HEPE or 18-HEPE-pretreated melanoma cells. Our results indicate that 18-HEPE is a potential anticancer metabolite that mediates, at least in part, the preventive effect of n-3 PUFA on melanoma metastasis.
Gradient Estimates on Dirichlet and Neumann Eigenfunctions
Authors: Arnaudon Marc , Thalmaier Anton , Wang Feng-Yu
Published: September 2018

By methods of stochastic analysis on Riemannian manifolds, we derive explicit constants $c_1(D)$ and $c_2(D)$ for a $d$-dimensional compact Riemannian manifold $D$ with boundary such that $c_1(D)\sqrt \lambda \|\phi \|_\infty \leqslant \|\nabla \phi \|_\infty \leqslant c_2(D)\sqrt \lambda \|\phi \|_\infty $ holds for any Dirichlet eigenfunction $\phi $ of $-\Delta $ with eigenvalue $\lambda $. In particular, when $D$ is convex with nonnegative Ricci curvature, the estimate holds for $c_1(D)= 1/{d\mathrm{e}}$ and $c_2(D)=\sqrt{\mathrm{e}}\left (\frac{\sqrt{2}}{\sqrt{\pi }}+\frac{\sqrt{\pi }}{4\sqrt{2}}\right ).$ Corresponding two-sided gradient estimates for Neumann eigenfunctions are derived in the second part of the paper.
Protonated CO2 in massive star-forming clumps
Authors: Fontani F , Vagnoli A , Padovani M , Colzi L , Caselli P , Rivilla V M
Published: September 2018

Interstellar CO2 is an important reservoir of carbon and oxygen, and one of the major constituents of the icy mantles of dust grains, but it is not observable directly in cold gas because it has no permanent dipole moment. Its protonated form, HOCO+, is believed to be a good proxy for gaseous CO2. However, it has been detected in only a few star-forming regions to date, so its interstellar chemistry is not well understood. We present new detections of HOCO+ lines in 11 high-mass star-forming clumps. Our observations more than treble the number of detections in star-forming regions to date. We derived beam-averaged abundances relative to H2 of between 0.3 and 3.8 × 10−11. We compared these values with the abundances of H13CO+, a possible gas-phase precursor of HOCO+, and of CH3OH, a product of surface chemistry. We found a positive correlation with H13CO+, but no correlation with CH3OH. We suggest that the gas-phase formation route starting from HCO+ plays an important role in the formation of HOCO+, perhaps more important than protonation of CO2 (upon evaporation of CO2 from icy dust mantles).
Observational evidence for extended emission to GW170817
Authors: van Putten Maurice H P M , Della Valle Massimo
Published: September 2018

The recent LIGO event GW170817 is the merger of a double neutron star system with an associated short GRB170817A with 2.9 ± 0.3 s soft emission over 8–70 keV. This association has a Gaussian equivalent level of confidence of 5.1σ. The merger produced a hypermassive neutron star or stellar mass black hole with prompt or continuous energy output powering GRB170817A. Here, we report on a possible detection of extended emission (EE) in gravitational radiation during GRB170817A: a descending chirp with characteristic time-scale $\tau _s=3.01\pm 0.2\,$ s in a (H1,L1)-spectrogram up to 700 Hz with Gaussian equivalent level of confidence greater than 3.3σ based on causality alone following edge detection applied to (H1,L1)-spectrograms merged by frequency coincidences. Additional confidence derives from the strength of this EE. The observed frequencies below 1 kHz indicate a hypermassive magnetar rather than a black hole, spinning down by magnetic winds and interactions with dynamical mass ejecta.
The phylogeny of Ryocalanoidea (Copepoda, Calanoida) based on morphology and a multi-gene analysis with a description of new ryocalanoidean species
Authors: Renz Jasmin , Markhaseva Elena L , Laakmann Silke
Published: September 2018

Two new species of ryocalanoid copepods (Crustacea: Calanoida), Ryocalanus squamatus sp. nov. and Yrocalanus kurilensis sp. nov. are described together with a female of Ryocalanus infelix Tanaka, 1956, type species for the genus Ryocalanus Tanaka, 1956, from abyssal depths in the Kurile-Kamchatka trench. The new species can be assigned to the superfamily Ryocalanoidea based on the segmentation and armature of the swimming legs and the modification of the male right antennule. A new interpretation of the fusions of segments in the male right antennule of Ryocalanus shows the marked differences between the ryocalanoidean genera. The status of Ryocalanoidea within the Calanoida is discussed based on morphology and a first molecular multi-gene analysis with cytochrome oxidase subunit I, cytochrome b, nuclear ribosomal 18S and 28S rDNA and internal transcribed spacer 2. This analysis supports the close interrelationship between Ryocalanoidea and Spinocalanoidea. The monophyletic status of Ryocalanoidea could not be retrieved in the phylogenetic analysis, as specimens of Yrocalanus formed a clade within Spinocalanoidea. The inconclusive results between morphological and molecular analyses are discussed with a proposition to keep the current system until more males of taxa belonging to the Spinocalanoidea are discovered, as the male antennule plays a crucial role in the interpretation of relationships between Ryocalanoidea and Spinocalanoidea.
Three-dimensional (3D) Printed Model to Plan the Endoscopic Treatment of Upper Airway Stenosis
Authors: Fiorelli Alfonso , Scaramuzzi Roberto , Minerva Ivana , De Ruberto Emanuele , Califano Teresa , Reginelli Alfonso , Grassi Roberto , Santini Mario
Published: September 2018

Background:

Endoscopic management of tracheal stenosis may be challenging, especially in the case of complex stenosis placed near the vocal folds, and needing stent placement. Herein, we evaluated the utility of the three-dimensional (3D) airway model for procedural planning in a consecutive series of patients with complex airway stenosis and scheduled for endoscopic treatment.

Methods:

This strategy was applied to 7 consecutive patients with tracheal stenosis unfit for surgery. The model was printed in a rubber-like material, and almost 7 hours were needed to create it. All patients presented respiratory failure with a mean value of 3.4±0.4 Medical Research Council (MRC) dyspnea scale, 47±3.9 forced expiratory volume in 1 second (FEV1%), and an impairment in the 6-minute walking test (6MWT) (mean value, 175±53 m). The mean length of the stenosis was 19±3.4 mm; 3 of the 7 (43%) patients presented a subglottic stenosis. In 4/7 (57%) patients the stenosis was >5 mm, but its treatment required the placement of a stent because of the presence of tracheal cartilage injury.

Results:

The mean operation time was 22.7±6.6 minutes. No complications were observed during and after the procedure. A significant increase of MRC (3.4±0.4 vs. 1.6±0.5; P=0.003), of FEV1% (47±3.9 vs. 77±9.7; P=0.001), and of 6MWT (175±53 vs. 423±101; P=0.0002) was observed after the procedure (mean follow-up, 11.1±8.8 mo).

Conclusion:

Our 3D airway model in the management of airway stenosis is useful for procedural planning, rehearsal, and education. The fidelity level of the 3D model remains the main concern for its wider use in patient care. Thus, our impressions should be confirmed by future prospective studies.
High-riding Superior Pericardial Recess
Authors: Kuperberg Stephen J. , Shostak Eugene
Published: September 2018

An understanding of thoracic computed tomographic anatomy is vital for procedural planning in bronchoscopy. When reviewing computed tomographic images in preparation for endobronchial ultrasound–directed staging for lung cancer, the presence of fluid in pericardial recesses can often be mistaken for mediastinal lymphadenopathy, potentially causing pitfalls in radiologic interpretation. We describe 2 cases of a high-riding superior aortic recess extending into right paratracheal lymph node station mimicking paratracheal lymphadenopathy. We review the anatomy and imaging characteristics of pericardial recesses with emphasis on differentiating these findings from mediastinal lymphadenopathy.
Capturing the global signature of surface ocean acidification during the Palaeocene–Eocene Thermal Maximum
Authors: Babila Tali L. , Penman Donald E. , Hönisch Bärbel , Kelly D. Clay , Bralower Timothy J. , Rosenthal Yair , Zachos James C.
Published: September 2018

Geologically abrupt carbon perturbations such as the Palaeocene–Eocene Thermal Maximum (PETM, approx. 56 Ma) are the closest geological points of comparison to current anthropogenic carbon emissions. Associated with the rapid carbon release during this event are profound environmental changes in the oceans including warming, deoxygenation and acidification. To evaluate the global extent of surface ocean acidification during the PETM, we present a compilation of new and published surface ocean carbonate chemistry and pH reconstructions from various palaeoceanographic settings. We use boron to calcium ratios (B/Ca) and boron isotopes (δ
11
B) in surface- and thermocline-dwelling planktonic foraminifera to reconstruct ocean carbonate chemistry and pH. Our records exhibit a B/Ca reduction of 30–40% and a δ
11
B decline of 1.0–1.2‰ coeval with the carbon isotope excursion. The tight coupling between boron proxies and carbon isotope records is consistent with the interpretation that oceanic absorption of the carbon released at the onset of the PETM resulted in widespread surface ocean acidification. The remarkable similarity among records from different ocean regions suggests that the degree of ocean carbonate change was globally near uniform. We attribute the global extent of surface ocean acidification to elevated atmospheric carbon dioxide levels during the main phase of the PETM.

This article is part of a discussion meeting issue ‘Hyperthermals: rapid and extreme global warming in our geological past’.
Sills and gas generation in the Siberian Traps
Authors: Svensen Henrik H. , Frolov Sergei , Akhmanov Grigorii G. , Polozov Alexander G. , Jerram Dougal A. , Shiganova Olga V. , Melnikov Nikolay V. , Iyer Karthik , Planke Sverre
Published: September 2018

On its way to the surface, the Siberian Traps magma created a complex sub-volcanic plumbing system. This resulted in a large-scale sill emplacement within the Tunguska Basin and subsequent release of sediment-derived volatiles during contact metamorphism. The distribution of sills and the released sediment-stored gas volume is, however, poorly constrained. In this paper, results from a study of nearly 300 deep boreholes intersecting sills are presented. The results show that sills with thicknesses above 100 m are abundant throughout the upper part of the sedimentary succession. A high proportion of the sills was emplaced within the Cambrian evaporites with average thicknesses in the 115–130 m range and a maximum thickness of 428 m. Thermal modelling of the cooling of the sills shows that the contact metamorphic aureoles are capable of generating 52–80 tonnes of CO
2
 m
−2
with contributions from both marine and terrestrial carbon. When up-scaling these borehole results, an area of 12–19 000 km
2
is required to generate 1000 Gt CO
2
. This represents only 0.7–1.2% of the total area in the Tunguska Basin affected by sills, emphasizing the importance of metamorphic gas generation in the Siberian Traps. These results strengthen the hypothesis of a sub-volcanic trigger and driver for the environmental perturbations during the End-Permian crisis.

This article is part of a discussion meeting issue ‘Hyperthermals: rapid and extreme global warming in our geological past’.
The extraterrestrial impact evidence at the Palaeocene–Eocene boundary and sequence of environmental change on the continental shelf
Authors: Schaller Morgan F. , Fung Megan K.
Published: September 2018

We have identified clear evidence of an extraterrestrial impact within the onset of the carbon isotope excursion (CIE) that defines the Palaeocene–Eocene (P-E) boundary hyperthermal event (approx. 56 Ma) from several sites on the eastern Atlantic Coastal Plain and offshore. We review and update the state of the evidence for an impact at the P-E boundary, including a K-Ar cooling age of the ejecta that is indistinguishable from the depositional age at the P-E, which establishes the ejecta horizon as an isochronous stratigraphic indicator at the P-E. Immediately above the ejecta peak at the base of the coastal plain Marlboro Clay unit, we identify a sharp increase in charcoal abundance coincident with the previously observed dramatic increase in magnetic nanoparticles of soil pyrogenic origin. We therefore revisit the observed sequence of events through the P-E boundary on the western Atlantic Coastal Plain, showing that an extraterrestrial impact led to wildfires, landscape denudation and deposition of the thick Marlboro Clay, whose base coincides with the spherule horizon and CIE onset. The Sr/Ca ratio of the spherules indicates that the carbon responsible for the onset may be vaporized CaCO
3
target rock mixed with isotopically light carbon from the impactor or elsewhere. Crucially, we do not argue that the impact was responsible for the full manifestation of the CIE observed globally (onset to recovery approx. 170 kyr), rather that a rapid onset was triggered by the impact and followed by additional carbon from other processes such as the eruption of the North Atlantic Igneous Province. Such a scenario agrees well with recent modelling work, though it should be revisited more explicitly.

This article is part of a discussion meeting issue ‘Hyperthermals: rapid and extreme global warming in our geological past’.
Eye-position error influence over “open-loop” smooth pursuit initiation
Authors: Buonocore Antimo , Skinner Julianne , Hafed Ziad M.
Published: September 2018

The oculomotor system integrates a variety of visual signals into appropriate motor plans, but such integration can have widely varying time scales. For example, smooth pursuit eye movements to follow a moving target are slower and longer-lasting than saccadic eye movements, and it has been suggested that initiating a smooth pursuit eye movement involves an obligatory open-loop interval, in which new visual motion signals presumably cannot influence the ensuing motor plan for up to 100 ms after movement initiation. However, this view runs directly contrary to the idea that the oculomotor periphery has privileged access to short-latency visual signals. Here we show that smooth pursuit initiation is sensitive to visual inputs, even in “open-loop” intervals. We instructed male rhesus macaque monkeys to initiate saccade-free smooth pursuit eye movements, and we injected a transient, instantaneous eye position error signal at different times relative to movement initiation. We found robust short-latency modulations in eye velocity and acceleration, starting only ∼50 ms after transient signal occurrence, and even during “open-loop” pursuit initiation. Critically, the spatial direction of the injected position error signal had predictable effects on smooth pursuit initiation, with forward errors increasing eye acceleration and backwards errors reducing it. Catch-up saccade frequencies and amplitudes were also similarly altered ∼50 ms after transient signals, much like well-known effects on microsaccades during fixation. Our results demonstrate that smooth pursuit initiation is highly sensitive to visual signals, and that catch-up saccade generation is reset after a visual transient.
Evolutionary design of regulatory control. II. Robust error-correcting feedback increases genetic and phenotypic variability
Authors: Frank Steven A.
Published: September 2018

As systems become more robust against perturbations, they can compensate for greater sloppiness in the performance of their components. That robust compensation reduces the force of natural selection on the system’s components, leading to component decay. The paradoxical coupling of robustness and decay predicts that robust systems evolve cheaper, lower performing components, which accumulate greater mutational genetic variability and which have greater phenotypic stochasticity in trait expression. Previous work noted the paradox of robustness. However, no general theory for the evolutionary dynamics of system robustness and component decay has been developed. This article takes a first step by linking engineering control theory with the genetic theory of evolutionary dynamics. Control theory emphasizes error-correcting feedback as the single greatest principle in robust system design. Linking control theory to evolution leads to a theory for the evolutionary dynamics of error-correcting feedback, a unifying approach for the evolutionary analysis of robust systems. In this article, I study how, in theory, increasingly robust systems accumulate more genetic variability and greater stochasticity of expression in their components. The theory predicts different levels of variability between different regulatory control architectures and different levels of variability between different components within a particular regulatory control system. Those predictions provide a way to understand the accumulating data on genetic variability and single-cell stochasticity of gene expression. I also show that increasing robustness reduces the frequency of system failures associated with disease and, simultaneously, causes a strong increase in the heritability of disease. Thus, robust error correction in biological regulatory control may partly explain the puzzlingly high heritability of disease and, more generally, the surprisingly high heritability of fitness.
Active sampling in visual search is coupled to the cardiac cycle
Authors: Galvez-Pol Alejandro , McConnell Ruth , Kilner James M.
Published: September 2018

Recent research has demonstrated that perception and reasoning vary according to the phase of internal bodily signals such as heartbeat. This has been shown by locking the presentation of sensory events to distinct phases of the cardiac cycle. However, task-relevant information is not usually encountered in such a phase-locked manner nor passively accessed, but rather actively sampled at one’s own pace. Moreover, if the phase of the cardiac cycle is an important modulator of perception and cognition, as previously proposed, then the way in which we actively sample the world should be similarly modulated by the phase of the cardiac cycle. Here we tested this by coregistration of eye movements and heartbeat signals while participants freely compared differences between two visual arrays. Across three different analyses, we found a significant coupling of saccades, subsequent fixations, and blinks with the cardiac cycle. More eye movements were generated during the systolic phase of the cardiac cycle, which has been reported as the period of maximal effect of the baroreceptors’ activity upon cognition. Conversely, more fixations were found during the diastole phase (quiescent baroreceptors). Lastly, more blinks were generated in the later period of the cardiac cycle. These results suggest that interoceptive and exteroceptive processing do adjust to each other; in our case, by sampling the outer environment during quiescent periods of the inner organism.
Live-cell single-molecule analysis of β2-adrenergic receptor diffusion dynamics and confinement
Authors: Schwenzer Niko , Bussmann Hendrik , Franken Sebastian , Häberlein Hanns
Published: September 2018

Signal transduction mechanisms and successive regulatory processes alter the lateral mobility of β2-adrenergic receptors (β2AR). In this work we combined modern single particle tracking methods in order to analyze the diffusion dynamics of SNAP-tagged β2AR in HEK wild-type cells and HEK β-arrestin knockout cells before and after agonist stimulation. For analysis of trajectories we first used mean squared displacement (MSD) analysis. Secondly, we applied an advanced variational Bayesian treatment of hidden Markov models (vbSPT) in combination with the recently introduced packing coefficient (Pc), which together provided a detailed model of three discrete diffusive states, state transitioning and spatial confinement. Interesting to note, state switching between S3 (fast-diffusing) and S1 (slow-diffusing) occurred sequentially over an intermediate state S2. After ligand stimulation more SNAP-tagged β2AR in HEK wild-type cells switched occupancy into the slow-diffusing state, whereas less receptors were found in the fast diffusive state. Unexpectedly, all three states showed a fraction of confined receptor mobility that increased under stimulation, but confinement sizes were unaffected. Receptor diffusion characteristics were comparable in HEK β-arrestin knockout cells under basal conditions and only minor but non-significant changes occurred upon stimulation, as expected from the depletion of β-arrestin, an important regulatory protein. The data presented here on the occurrence of different diffusion states, their transitioning and variable spatial confinements clearly indicate that lateral mobility of β2AR is much more complex than previously thought.
Alterations in swimming behavior of Daphnia exposed to polymer and mineral particles: towards understanding effects of microplastics on planktonic filtrators
Authors: Gorokhova E. , Könnecke O. , Ogonowski M. , Gerdes Z. , Eriksson Wiklund AK
Published: September 2018

Concerns have been raised that microplastics (MP) can impact aquatic organisms by compromising their nutrition. However, little is understood about the mechanisms of the adverse effects of MP in suspension-feeders that routinely ingest particles of low nutritional value, such as mineral particles. We compared effects of non-edible particles (MP and kaolin) mixed with microalgae on the swimming and filtering behavior of a planktonic filtrator Daphnia magna; incubations with only algae served as controls. The following questions were addressed: (1) Are there differences in swimming movements between the daphnids exposed to MP and those exposed to kaolin? and (2) Whether occurrence of biofilm on the particle surface affects daphnid swimming and how these effects differ between the kaolin- and MP-exposed animals? We found that both kaolin and MP altered swimming, yet in opposite way, with a decrease of filtration-related movements in kaolin and their increase in MP. The difference was amplified in biofilm coated particles, indicating that daphnids spend more energy when swimming in suspension with MP, and even more when the MP have biofilm. The increased swimming activity of filtrators exposed to plastic litter decaying to microparticles may translate into changes in energy balance and growth.
EEG-based age-prediction models as stable and heritable indicators of brain maturational level in children and adolescents
Authors: Vandenbosch Marjolein M.L.J.Z. , van’t Ent Dennis , Boomsma Dorret I. , Anokhin Andrey P. , Smit Dirk J.A.
Published: September 2018

The human brain shows remarkable development of functional brain activity from childhood to adolescence. Here, we investigated whether electroencephalogram (EEG) recordings are suitable for predicting the age of children and adolescents. Moreover, we investigated whether over-or underestimation of age was stable over longer time periods, as stable prediction error can be interpreted as reflecting individual brain maturational level. Finally, we established whether the age-prediction error was genetically determined. Three minutes eyes-closed resting state EEG data from the longitudinal EEG studies of Netherlands Twin Register (n=836) and Washington University in St. Louis (n = 702) were used at ages 5, 7, 12, 14, 16 and 18. Longitudinal data were available within childhood and adolescence. We calculated power in 1 Hz wide bins (1 to 24 Hz). Random Forest regression and Relevance Vector Machine with 6-fold cross-validation were applied. The best mean absolute prediction error was obtained with Random Forest (1.22 years). Classification of childhood vs. adolescence reached over 94% accuracy. Prediction errors were moderately to highly stable over periods of 1.5 to 2.1 years (0.53 < r < 0.74) and signifcantly affected by genetic factors (heritability between 42% and 79%). Our results show that age prediction from low-cost EEG recordings is comparable in accuracy to those obtained with MRI. Children and adolescents showed stable over- or underestimation of their age, which means that some participants have stable brain activity patterns that reflect those of an older or younger age, and could therefore reflect individual brain maturational level. This prediction error is heritable, suggesting that genes underlie maturational level of functional brain activity. We propose that age prediction based on EEG recordings can be used for tracking neurodevelopment in typically developing children, in preterm children, and in children with neurodevelopmental disorders.
The effects of in-vitro pH decrease on the gametogenesis of the red tree coral, Primnoa pacifica
Authors: Rossin Ashley M , Waller Rhian G , Stone Robert P
Published: September 2018

Primnoa pacifica is the most ecologically important coral species in the North Pacific Ocean where it provides important habitat for commercially important fish and invertebrates. Ocean acidification (OA) is more rapidly increasing in high-latitude seas because anthropogenic CO2 uptake is greater in these regions. This is due to the solubility of CO2 in cold water and the reduced buffering capacity due to low alkalinity of colder waters. Primnoa pacifica colonies were cultured for six to nine months in either pH 7.55 (predicted 2100 pH levels) or pH 7.75 (control). Oocyte development and fecundity in females, and spermatocyst stages in males were measured to assess the effects of pH on gametogenesis. Oocyte diameters were 13.6% smaller and fecundities were 30.9% lower in the Year 2100 samples, indicating that OA may limit oocyte formation, potentially through lipid limitation. A higher proportion of vitellogenic oocytes (65%) were also reabsorbed (oosorption) in the Year 2100 treatment. Lowered pH appeared to advance the process of spermatogenesis with a higher percentage of later stage sperm compared to control controls. There was a laboratory effect observed in all measurement types, however these only significantly affected the analyses of spermatogenesis. These results indicate that reproduction may not be possible in an acidified ocean, or that if spawning could occur, spawned oocytes would not be sufficiently equipped to support the normal development of larvae.
Staphylococcus aureuslipase: purification, kinetic characterization, crystallization and crystallographic study
Authors: Tanaka Mutsumi , Kamitani Shigeki , Kitadokoro Kengo
Published: September 2018

Staphylococcus aureuslipase (SAL), a triacylglycerol esterase, is an important virulence factor inS. aureusand may be a therapeutic target for infectious diseases caused byS. aureus. For the purposes of anti-SAL drug development using structure-based drug design, X-ray crystallographic analysis of SAL overexpressed inEscherichia coliwas performed. The recombinant protein was purified using a three-step protocol involving immobilized metal-affinity chromatography, cation-exchange chromatography and anion-exchange chromatography flowthrough methods, yielding 40 mg of protein per litre of bacterial culture. Crystals were obtained using the sitting-drop vapor-diffusion technique. Diffraction data to 3.0 Å resolution were collected on the BL44XU beamline at SPring-8 at the zinc peak of 1.2842 Å for SAD phasing. The crystals belonged to space groupP4122 orP4322, with unit-cell parametersa= 131.0,b = 131.0,c = 250.6 Å, and are likely to contain four SAL molecules (408 residues) per asymmetric unit.
Crystal structure of the post-fusion core of theHuman coronavirus 229Espike protein at 1.86 Å resolution
Authors: Yan Lei , Meng Bing , Xiang Jiangchao , Wilson Ian A. , Yang Bei
Published: September 2018

Human coronavirus 229E(HCoV-229E) usually causes mild upper respiratory infections in heathy adults, but may lead to severe complications or mortality in individuals with weakened immune systems. Virus entry of HCoV-229E is mediated by its spike (S) protein, where the S1 domain facilitates attachment to host cells and the S2 domain is involved in subsequent fusion of the virus and host membranes. During the fusion process, two heptad repeats, HR1 and HR2, in the S2 domain assemble into a six-helix membrane-fusion structure termed the fusion core. Here, the complete fusion-core structure of HCoV-229E has been determined at 1.86 Å resolution, representing the most complete post-fusion conformation thus far among published human alphacoronavirus (α-HCoV) fusion-core structures. The overall structure of the HCoV-229E fusion core is similar to those of SARS, MERS and HCoV-NL63, but the packing of its 3HR1 core differs from those of SARS and MERS in that it contains more noncanonical `x' and `da' layers. Side-by-side electrostatic surface comparisons reveal that the electrostatic surface potentials are opposite in α-HCoVs and β-HCoVs at certain positions and that the HCoV-229E surface also appears to be the most hydrophobic among the various HCoVs. In addition to the highly conserved hydrophobic interactions between HR1 and HR2, some polar and electrostatic interactions are also well preserved across different HCoVs. This study adds to the structural profiling of HCoVs to aid in the structure-based design of pan-coronavirus small molecules or peptides to inhibit viral fusion.
Improving signal strength in serial crystallography with DIALS geometry refinement
Authors: Brewster Aaron S. , Waterman David G. , Parkhurst James M. , Gildea Richard J. , Young Iris D. , O'Riordan Lee J. , Yano Junko , Winter Graeme , Evans Gwyndaf , Sauter Nicholas K.
Published: September 2018

The DIALS diffraction-modeling software package has been applied to serial crystallography data. Diffraction modeling is an exercise in determining the experimental parameters, such as incident beam wavelength, crystal unit cell and orientation, and detector geometry, that are most consistent with the observed positions of Bragg spots. These parameters can be refined by nonlinear least-squares fitting. In previous work, it has been challenging to refine both the positions of the sensors (metrology) on multipanel imaging detectors such as the CSPAD and the orientations of all of the crystals studied. Since the optimal models for metrology and crystal orientation are interdependent, alternate cycles of panel refinement and crystal refinement have been required. To simplify the process, a sparse linear algebra technique for solving the normal equations was implemented, allowing the detector panels to be refined simultaneously against the diffraction from thousands of crystals with excellent computational performance. Separately, it is shown how to refine the metrology of a second CSPAD detector, positioned at a distance of 2.5 m from the crystal, used for recording low-angle reflections. With the ability to jointly refine the detector position against the ensemble of all crystals used for structure determination, it is shown that ensemble refinement greatly reduces the apparent nonisomorphism that is often observed in the unit-cell distributions from still-shot serial crystallography. In addition, it is shown that batching the images by timestamp and re-refining the detector position can realistically model small, time-dependent variations in detector position relative to the sample, and thereby improve the integrated structure-factor intensity signal and heavy-atom anomalous peak heights.
New tools for the analysis and validation of cryo-EM maps and atomic models
Authors: Afonine Pavel V. , Klaholz Bruno P. , Moriarty Nigel W. , Poon Billy K. , Sobolev Oleg V. , Terwilliger Thomas C. , Adams Paul D. , Urzhumtsev Alexandre
Published: September 2018

Recent advances in the field of electron cryomicroscopy (cryo-EM) have resulted in a rapidly increasing number of atomic models of biomacromolecules that have been solved using this technique and deposited in the Protein Data Bank and the Electron Microscopy Data Bank. Similar to macromolecular crystallography, validation tools for these models and maps are required. While some of these validation tools may be borrowed from crystallography, new methods specifically designed for cryo-EM validation are required. Here, new computational methods and tools implemented inPHENIXare discussed, includingd99to estimate resolution,phenix.auto_sharpento improve maps andphenix.mtriageto analyze cryo-EM maps. It is suggested that cryo-EM half-maps and masks should be deposited to facilitate the evaluation and validation of cryo-EM-derived atomic models and maps. The application of these tools to deposited cryo-EM atomic models and maps is also presented.
Impacts of DNA extraction and PCR on DNA metabarcoding estimates of soil biodiversity
Authors: Dopheide Andrew , Xie Dong , Buckley Thomas R. , Drummond Alexei J. , Newcomb Richard D.
Published: September 2018

Soils are ubiquitous and important components of terrestrial ecosystems, richly populated with diverse organisms with important ecological roles. DNA metabarcoding is a promising tool for efficient and taxonomically comprehensive analyses of soil biodiversity, but the outcomes of these analyses are likely affected by basic methodological factors such as sampling and laboratory protocols.

We investigated the impacts of DNA extraction methodology and multiple PCRs on DNA metabarcoding biodiversity estimates for multiple taxonomic groups in soil. We applied four DNA extraction methods with different size constraints in parallel to fixed volumes of soil from a pair of forest sites, followed by sets of ten individually indexed PCRs and Illumina sequencing of prokaryote (16S) and eukaryote (18S, fungal 26S, and metazoan cytochrome c oxidase subunit I) barcodes.

Methods utilizing larger soil volumes resulted in higher biodiversity estimates for arthropods but not for prokaryotes or microeukaryotes, and improved spatial discrimination of metazoan communities but not prokaryotes. Each DNA extraction method resulted in a biased community composition, and these biases were consistent across sites and amplicons. Some 36%–41% of operational taxonomic units (OTUs) were shared between all four DNA extraction methods and OTUs from many phyla had contrasting abundances from different methods. From 0.2% to 19% of OTUs, accounting for 9.4% to 97% of sequence reads, were amplified in all 10 PCRs from each DNA extraction method and sample. OTUs detected in only a single PCR accounted for 26% to 41% of OTUs but only 0.3% to 2.8% of the sequence reads from each extraction method and sample. The inferred species richness increased strongly with the number of PCRs carried out.

We conclude that a consistent DNA extraction method should be used for comparisons between samples, confirm that larger samples of soil (≥15 g) should be used for analyses of metazoan biodiversity than for microbes, and that the number of PCR replicates undertaken strongly affects species richness estimates.
Does per‐act HIV‐1 transmission risk through anal sex vary by gender? An updated systematic review and meta‐analysis
Authors: Baggaley Rebecca F. , Owen Branwen N. , Silhol Romain , Elmes Jocelyn , Anton Peter , McGowan Ian , van der Straten Ariane , Shacklett Barbara , Dang Que , Swann Edith M. , Bolton Diane L. , Boily Marie‐Claude
Published: September 2018

Quantifying HIV‐1 transmission risk per‐act of anal intercourse (AI) is important for HIV‐1 prevention. We updated previous reviews by searching Medline and Embase to 02/2018. We derived pooled estimates of receptive AI (URAI) and insertive AI (UIAI) risk unprotected by condoms using random‐effects models. Subgroup analyses were conducted by gender, study design, and whether antiretroviral treatment (ART) had been introduced by the time of the study. Two new relevant studies were identified, one of which met inclusion criteria, adding three new cohorts and increasing number of individuals/partnerships included from 1869 to 14 277. Four studies, all from high‐income countries, were included. Pooled HIV‐1 risk was higher for URAI (1.25%, 95% CI 0.55%‐2.23%, N = 5, I2 = 87%) than UIAI (0.17%, 95 % CI 0.09%‐0.26%, N = 3, I2 = 0%). The sole heterosexual URAI estimate (3.38%, 95% CI 1.85%‐4.91%), from a study of 72 women published in a peer‐reviewed journal, was significantly higher than the men‐who‐have‐sex‐with‐men (MSM) pooled estimate (0.75%, 95% CI 0.56%‐0.98%, N = 4, P < 0.0001) and higher than the only other heterosexual estimate identified (0.4%, 95% CI 0.08%‐2.0%, based on 59 women, excluded for being a pre‐2013 abstract). Pooled per‐act URAI risk varied by study design (retrospective‐partner studies: 2.56%, 95% CI 1.20%‐4.42%, N = 2 (one MSM, one heterosexual); prospective studies: 0.71%, 95% CI 0.51%‐0.93%, N = 3 MSM, P < 0.0001). URAI risk was lower for studies conducted in the ART era (0.75%, 95% CI 0.52%‐1.03%) than pre‐ART (1.67%, 95% CI 0.44%‐3.67%) but not significantly so (P = 0.537). Prevention messages must emphasize that HIV‐1 infectiousness through AI remains high, even in the ART era. Further studies, particularly among heterosexual populations and in resource‐limited settings, are required to elucidate whether AI risk differs by gender, region and following population‐level ART scale‐up.
Mitigating the urban–rural educational gap in developing countries through mobile technology‐supported learning
Authors: Khan Sharifullah , Hwang Gwo‐Jen , Azeem Abbas Muhammad , Rehman Arshia
Published: September 2018

One form of educational inequality is the disparity that exists between urban and rural settings. Equal distribution of quality education is a challenge for developing countries due to the unavailability of resources. Various approaches to equal distribution are distance learning, telecast learning and e‐learning; however, these approaches cannot achieve the desired objectives due to their limitations. This research aimed to investigate the interesting question of whether mobile technology can bring urban and rural settings closer together. A mobile application for learning Urdu grammar was designed to measure the learning gains of fourth‐grade students at two different schools from urban and rural settings. A quantitative technique, the quasi‐experimental pre‐test and post‐test method, was used to measure the effectiveness of the mobile application. The comparison of the students’ performances at the urban and rural schools illustrated the role of mobile technology in mitigating the educational gap. The present study provides evidence that children from different social backgrounds may benefit equally from mobile technology.
Sexual freedoms
Authors: Stjerna Kirsi
Published: September 2018

Women—still—experience different forms of sexism in their daily lives. After the sixteenth‐century Protestant proclamation of the blessings of motherhood and women's bodies, and the women's sexual liberation movement of the 1960s, women's real freedoms and rights with their bodies, including sexual relations and procreation, are still being negotiated. Violence against women's bodies, including sex trafficking, relates to both the lack of appropriate education and fundamentally distorted views of humanity. Considering Luther's teaching on women as imago Dei, and attending theologically to the issues pertaining to misogyny—such as reforming the traditionally male‐centered God‐language and challenging the culture's implicit permission for ongoing violence against women—are some of the concrete steps that can be taken. Given the revelations with the #MeToo movement, the ELCA's 2018 draft on the Social Statement on Gender and Justice is timely.
Responses to the ELCA “Draft social statement on women and justice”
Authors: Streufert Mary J. , Blasi Marcia , Crist Jessica , Graybill Rhiannon , Yip Man‐Hei
Published: September 2018

Social statements are social teaching and policy documents in the Evangelical Lutheran Church in America. Created by task forces composed of ELCA members and supported by ELCA churchwide staff members, social statements are developed through a series of participatory steps. Contributors in this work share their feedback on the “Draft Social Statement on Women and Justice” with the task force as part of the process to create a proposed social statement for an assembly vote.
Prevalence and predictors of delayed clinical diagnosis of Type 2 diabetes: a longitudinal cohort study
Authors: Gopalan A. , Mishra P. , Alexeeff S. E. , Blatchins M. A. , Kim E. , Man A. H. , Grant R. W.
Published: September 2018

Aims

To examine the prevalence and person‐level predictors of undiagnosed Type 2 diabetes among adults with elevated HbA1c values.

Methods

We identified adults without diabetes who had a first elevated HbA1c (index HbA1c ≥ 48 mmol/mol; ≥ 6.5%) between January 2014 and December 2015, and classified them by Type 2 diabetes diagnosis status at 1 year following this result. Multilevel modelling techniques were used to examine the association of individual demographic, clinical, and utilization characteristics with remaining undiagnosed. We quantified differences in early Type 2 diabetes care between diagnosed and undiagnosed individuals.

Results

Of the 18 356 adults with a first elevated index HbA1c, 30.2% remained undiagnosed with Type 2 diabetes 1 year later. Individuals with lower index HbA1c values [adjusted odds ratio (aOR) 5.95, 95% confidence interval (CI) 5.21–6.78 for 48 to <53 mmol/mol (6.5% to 7.0%); referent 53 to <64 mmol/mol (7.0% to <8.0%)], who were ≥ 70 years old (aOR 1.40, 95% CI 1.24–1.59; referent 50–59 years), and who had a prior prediabetes diagnosis (aOR 1.35, 95% CI 1.24–1.47; referent no prediabetes) had increased odds of remaining undiagnosed. After adjusting for age, race, and index HbA1c, remaining undiagnosed was associated with lower odds of initiating metformin (aOR 0.06, 95% CI 0.05–0.07).

Conclusions

Almost one‐third of adults with an elevated HbA1c value were not diagnosed with Type 2 diabetes within 1 year. Undiagnosed Type 2 diabetes, in turn, was associated with differences in early care. Strategies that leverage the electronic health record to facilitate earlier diagnosis may help reduce delays and allow for early intervention towards the goal of improved outcomes.
Prospective memory in individuals with first‐episode schizophrenia: A two‐year longitudinal study
Authors: Cheung Eric F. C. , Lui Simon S. Y. , Wang Ya , Liu Amy C. Y. , Chui William W. H. , Yeung Hera K. H. , Yang Tian‐Xiao , Shum David H. K. , Chan Raymond C. K.
Published: September 2018

Aim

The present study aimed to explore the two‐year naturalistic trajectory of time‐ and event‐based prospective memory (PM) in patients with first‐episode schizophrenia.

Methods

We administered a computer‐based dual‐task PM paradigm to 57 individuals with first‐episode schizophrenia at baseline and after 6 months, 12 months and 24 months. Forty‐eight healthy controls were also recruited and completed all the measures at baseline. We compared the trajectories between time‐based and event‐based PM in first‐episode schizophrenia patients using repeated measures ANOVAs, and examined the relationship between PM and clinical symptoms using Spearman's correlation.

Results

PM impairments improved significantly after 24 months of follow‐up. However, time‐based and event‐based PM appeared to run different trajectories. After 24 months, first‐episode schizophrenia patient performed poorer than healthy controls in time‐based but not event‐based PM. PM did not appear to be correlated with clinical symptoms, both cross‐sectionally and longitudinally.

Conclusions

This is one of the longest follow‐up studies investigating PM in first‐episode schizophrenia. Our results provide evidence to support that time‐based PM is more temporally stable than event‐based PM.