bluuebunny/crossref_metadata_2025 huggingface dataset:
2459 Hippocampal network disruption in early amyloid pathology
Authors: Caccavano Adam , Vicini Stefano
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: We aim to show that amyloid accumulation in an animal model of Alzheimer’s disease leads to a preferential disruption of inhibitory parvalbumin-expressing interneurons, and the peri-neuronal nets that surround them, resulting in downstream network alterations to potentially explain early mechanisms of memory impairment in the disease. METHODS/STUDY POPULATION: We employ the 5xFAD mouse model of familial Alzheimer’s disease crossed with transgenic mouse lines which fluoresce red or green in specific neuronal populations. We conducted immunostaining and immunoblotting in amyloid accumulating animals compared with healthy littermate control. Future experiments will be performed in human postmortem tissue to translate these results from mouse model to the human population. Electrophysiological recordings from acute mouse brain slices were conducted as a functional assay. RESULTS/ANTICIPATED RESULTS: Preliminary results indicate that PNNs are disrupted and that activity-associated levels of PV are reduced. Both inhibitory PV and excitatory pyramidal cell populations exhibit altered spiking and synaptic activity during sharp wave ripple events. DISCUSSION/SIGNIFICANCE OF IMPACT: By elucidating the specific neuronal sub-type that is responsible for hippocampal network disruption, future studies could attempt a targeted optogenetic or pharmacological intervention to restore network activity important for memory consolidation.
Adjoint-based parametric sensitivity analysis for swirling M-flames
Authors: Skene Calum S. , Schmid Peter J.
Published: November 2018

A linear numerical study is conducted to quantify the effect of swirl on the response behaviour of premixed lean flames to general harmonic excitation in the inlet, upstream of combustion. This study considers axisymmetric M-flames and is based on the linearised compressible Navier–Stokes equations augmented by a simple one-step irreversible chemical reaction. Optimal frequency response gains for both axisymmetric and non-axisymmetric perturbations are computed via a direct–adjoint methodology and singular value decompositions. The high-dimensional parameter space, containing perturbation and base-flow parameters, is explored by taking advantage of generic sensitivity information gained from the adjoint solutions. This information is then tailored to specific parametric sensitivities by first-order perturbation expansions of the singular triplets about the respective parameters. Valuable flow information, at a negligible computational cost, is gained by simple weighted scalar products between direct and adjoint solutions. We find that for non-swirling flows, a mode with azimuthal wavenumber $m=2$ is the most efficiently driven structure. The structural mechanism underlying the optimal gains is shown to be the Orr mechanism for $m=0$ and a blend of Orr and other mechanisms, such as lift-up, for other azimuthal wavenumbers. Further to this, velocity and pressure perturbations are shown to make up the optimal input and output showing that the thermoacoustic mechanism is crucial in large energy amplifications. For $m=0$ these velocity perturbations are mainly longitudinal, but for higher wavenumbers azimuthal velocity fluctuations become prominent, especially in the non-swirling case. Sensitivity analyses are carried out with respect to the Mach number, Reynolds number and swirl number, and the accuracy of parametric gradients of the frequency response curve is assessed. The sensitivity analysis reveals that increases in Reynolds and Mach numbers yield higher gains, through a decrease in temperature diffusion. A rise in mean-flow swirl is shown to diminish the gain, with increased damping for higher azimuthal wavenumbers. This leads to a reordering of the most effectively amplified mode, with the axisymmetric ($m=0$) mode becoming the dominant structure at moderate swirl numbers.
Locomotion of a single-flagellated bacterium
Authors: Park Yunyoung , Kim Yongsam , Lim Sookkyung
Published: November 2018

Single-flagellated bacteria propel themselves by rotating a flagellar motor, translating rotation to the filament through a compliant hook and subsequently driving the rotation of the flagellum. The flagellar motor alternates the direction of rotation between counterclockwise and clockwise, and this leads to the forward and backward directed swimming. Such bacteria can change the course of swimming as the hook experiences its buckling caused by the change of bending rigidity. In this paper, we present a comprehensive model of a monotrichous bacterium as a free swimmer in a viscous fluid. We describe a cell body as a rigid body using the penalty method and a flagellum as an elastic rod using Kirchhoff rod theory. The hydrodynamic interaction of the bacterium is described by the regularized Stokes formulation. Our model of a single-flagellated micro-organism is able to mimic a swimming pattern that is well matched with the experimental observation. Furthermore, we find the critical thresholds of the rotational frequency of the motor and the bending modulus of the hook for the buckling instability, and investigate the dependence of the buckling angle and the reorientation of the swimming cell after buckling on the physical and geometrical parameters of the model.
Deformation of a linear viscoelastic compliant coating in a turbulent flow
Authors: Benschop H. O. G. , Greidanus A. J. , Delfos R. , Westerweel J. , Breugem W.-P.
Published: November 2018

We investigate the deformation of a linear viscoelastic compliant coating in a turbulent flow for a wide range of coating parameters. A one-way coupling model is proposed in which the turbulent surface stresses are expressed as a sum of streamwise-travelling waves with amplitudes determined from the stress spectra of the corresponding flow over a rigid wall. The analytically calculated coating deformation is analysed in terms of the root-mean-square (r.m.s.) surface displacement and the corresponding point frequency spectra. The present study systematically investigates the influence of five coating properties namely density, stiffness, thickness, viscoelasticity and compressibility. The surface displacements increase linearly with the fluid/solid density ratio. They are linearly proportional to the coating thickness for thin coatings, while they become independent of the thickness for thick coatings. Very soft coatings show resonant behaviour, but the displacement for stiffer coatings is proportional to the inverse of the shear modulus. The viscoelastic loss angle has only a significant influence when resonances occur in the coating response, while Poisson’s ratio has a minor effect for most cases. The modelled surface displacement is qualitatively compared with recent measurements on the deformation of three different coatings in a turbulent boundary-layer flow. The model predicts the order of magnitude of the surface displacement, and it captures the increase of the coating displacement with the Reynolds number and the coating softness. Finally, we propose a scaling that collapses all the experimental data for the r.m.s. of the vertical surface displacement onto a single curve.
Turbulent structures in a statistically three-dimensional boundary layer
Authors: Kevin Kevin , Monty Jason , Hutchins Nicholas
Published: November 2018

We investigate the behaviour of large-scale coherent structures in a spanwise-heterogeneous turbulent boundary layer, using particle image velocimetry on multiple orthogonal planes. The statistical three-dimensionality is imposed by a herringbone riblet surface, although the key results presented here will be common to many cases of wall turbulence with embedded secondary flows in the form of mean streamwise vortices. Instantaneous velocity fields in the logarithmic layer reveal elongated low-momentum streaks located over the upwash-flow region, where their spanwise spacing is forced by the$2\unicode[STIX]{x1D6FF}$periodicity of the herringbone pattern. These streaks largely resemble the turbulence structures that occur naturally (and randomly located) in spanwise-homogeneous smooth-/rough-wall boundary layers, although here they are directly formed by the roughness pattern. In the far outer region, the large spanwise spacing permits the streaks to aggressively meander. The mean secondary flows are the time-averaged artefact of the unsteady and spanwise asymmetric large-scale roll modes that accompany these meandering streaks. Interestingly, this meandering, or instability, gives rise to a pronounced streamwise periodicity (i.e. an alternating coherent pattern) in the spatial statistics, at wavelengths of approximately 4.5$\unicode[STIX]{x1D6FF}$. Overall, the observed behaviours largely resemble the streak-instability model that has been proposed for the buffer region, only here at a much larger scale and at a forced spanwise spacing. This observation further confirms recent observations that such features may occur at an entire hierarchy of scales throughout the turbulent boundary layer.
The disappearance of the sacred Swedish Sámi drum and the protection of Sámi cultural heritage
Authors: Joy Francis
Published: November 2018

One of the last frontiers of the pre-Christian Sámi religion and cosmology from the seventeenth and eighteenth centuries can be found recorded as embedded systems of knowledge on a range of noaidi-shaman drums kept in museums across Europe. Missionaries and clergymen as well as explorers who sought interest in the magical powers of the Sámi noaidi collected these artefacts during witchcraft trials and persecutions throughout Sápmi, the Sámi homeland areas. Insomuch as the drums being taken away from their owners and shipped from their homelands to other countries, their safeguarding, security and preservation as ancient sources of knowledge in museums is seldom discussed. As a consequence, the investigation presented here is a case study concerning the disappearance of a Sámi noaidi drum sent to a museum in France that has its origins in Swedish Sápmi, which I was informed about in 2017 prior to a visit to Paris for a seminar concerning the Sámi and their culture in Finland. The loss of the drum has only recently become known, and raises a series of important questions concerning responsibilities museums have with regard to the protection of property belonging to the Sámi as well as the repatriation and return of cultural heritage with regard to historical artefacts.
Crystal structure of minocycline hydrochloride dihydrate form A, C23H28N3O7Cl (H2O)2
Authors: Wheatley Austin M. , Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: November 2018

The crystal structure of minocycline hydrochloride dihydrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Minocycline hydrochloride dihydrate crystallizes in space groupP212121(#19) witha= 7.40772(1),b= 14.44924(3),c= 22.33329(4) Å,V= 2390.465(12) Å3, andZ= 4. The minocycline cation is a zwitterion: both dimethylamino groups are protonated and one hydroxyl group is ionized. A potential ambiguity in the orientation of the amide group was resolved by considering Rietveld refinement residuals and displacement coefficients, as well as DFT energies. The crystal structure is dominated by hydrogen bonds. Both water molecules and a hydroxyl group act as donors to the chloride anion. Both protonated dimethyl amine groups act as donors to the ionized hydroxyl group. Several intramolecular O–H···O hydrogen groups help determine the conformation of the cation. The powder pattern is included in the Powder Diffraction File™ as entry 00-066-1606.
Effects of transportation on cattle health and production: a review
Authors: Van Engen N. K. , Coetzee J. F.
Published: November 2018

The goal of this review is to present a concise and critical assessment of the literature related to physiologic responses in cattle that are subjected to transportation. Over two-thirds of US cattle are transported. Understanding trends in circulating physiologic parameters is an important part of mitigating the negative effects of transportation. For the producer, linking these effects after transportation to morbidity outcomes within the first 45 days on feed (i.e. especially development of bovine respiratory disease) is critical. Physiologic parameters in circulation are of primary importance and may have value for prediction of bovine respiratory disease on arrival and for the understanding of disease pathogenesis. The results of our literature survey indicated that post-transportation immune function, increased acute phase proteins, glucocorticoids, and inflammation are a pivotal starting point for understanding disease. These potential biomarkers may have utility in identifying disease for targeted therapeutics so that traditional protocols that rely heavily on metaphylaxis can be avoided. Additional research is needed to develop strategies for physiological marker identification, treatment methods, or predictive behaviors to prevent respiratory disease before and after transport. This review examines the significant deleterious effects of transportation handling and stress, and current immune system translation and non-antimicrobial mitigation strategies.
The State of Emergency in France: Days Without End?
Authors: Vauchez Stéphanie Hennette
Published: November 2018

State of emergency in France – Historical origins of the legal regime – Ways in which it was adapted and normalised between 2015 and 2017 – Application against rule of law principles and human rights standards – Institutional balance between powers – In-depth study of 700 court decisions – Legal challenges to state of emergency measures – Challenges to judicial scrutiny
A changing economic vote in Western Europe? Long-term vs. short-term forces
Authors: Dassonneville Ruth , Lewis-Beck Michael S.
Published: November 2018

Considerable research shows the presence of an economic vote, with governments rewarded or punished by voters, depending on the state of the economy. But how stable is this economic vote? A current argument holds its effect has increased over time, because of weakening long-term social and political forces. Under these conditions, short-term forces, foremostly the economic issue, can come to the fore. A counter-argument, however, sees the economic vote effect in decline, due to globalization. Against these rival hypotheses rests the status-quo argument: the economic vote effect remains unchanged. To test these claims, we estimate carefully specified models of the incumbent vote, at both the individual and aggregate levels. Western European elections provide the data, with particular attention to Denmark, Germany, Great Britain, Italy, The Netherlands, Norway, and Sweden. Perhaps surprisingly, we find the economic vote to be stable over time, a ‘standing decision’ rule that voters follow in national elections.
Differential Response of Fall Panicum (Panicum dichotomiflorum) Populations in Florida Sugarcane to Asulam
Authors: Fernandez Jose V. , Odero D. Calvin , MacDonald Gregory E. , Ferrell Jason A. , Sellers Brent A. , Wilson P. Christopher
Published: November 2018

Sugarcane growers in Florida have been reporting reduced control of fall panicum with asulam, the main herbicide used for POST grass control. Therefore, outside container experiments were conducted to determine the response of four fall panicum populations from Florida to asulam applied alone and to evaluate whether tank-mix combination with trifloxysulfuron enhances control. Asulam was applied at 230 to 7,400 g ai ha−1, corresponding to 1/16 to 2X the maximum labeled rate for a single application in sugarcane, with or without combination with trifloxysulfuron at 16 g ai ha−1. Three fall panicum populations were collected from fields in which reduced control had been reported, while one population was from a field not used for sugarcane production but adjacent to a sugarcane field. The potency of asulam based on ED50values (the rate required to cause 50% dry weight reduction at 28 d after treatment) ranged from 2,249 to 5,412 g ha−1for tolerant populations with reported reduced fall panicum control compared with 1,808 g ha−1for the susceptible population from the field not used for sugarcane production, showing that the latter was most sensitive to asulam. Addition of trifloxysulfuron to asulam increased potency on fall panicum by 5- to 15-fold, indicating that the tank mix enhanced dry weight reduction for all populations. The probability of fall panicum survival (regrowth after aboveground biomass harvesting) at the labeled rate of asulam ranged from 2% to 47% compared with 0% to 6% when trifloxysulfuron was added to the tank mix. Our results show differential response of fall panicum populations in Florida to asulam, which can be overcome by tank mixing with trifloxysulfuron even for populations that are difficult to control in sugarcane, but no evolution of resistance to asulam.
Effects of Shape and Rotation of Sand Particles in Saltation
Authors: Dun Hongchao , Huang Ning , Zhang Jie , He Wei
Published: November 2018

Eolian sand transport is a typical gas‐solid flow process, and saltating sand particles account for 75% of the total sand transported. Sand particles are considered as perfect spheres, and the forces acted on the particles are calculated using concise formulas in almost all wind‐sand movement models. In fact, most of sand particles in natural environment are nonspherical and usually rotating while they saltate in the air, and the complicated turbulent gas‐solid flow caused by irregular shape and rotation of particles cannot be predicted. In this paper, the microcosmic midair movements of rotating elliptical sand particles are simulated with dynamic grid method, and the interaction between airflow and sand particles is studied. The results show that the trajectory of a rotating elliptical particle is 18.8% higher and 31.8% longer than that of a spherical one and the drag force acted on a rotating elliptical sand particle fluctuates periodically over time. Separating, colliding, and tumbling behaviors are observed during the saltation process of coupled sand particles. Affected by strong interaction between rotating coupled elliptical particles and airflow, the trajectory is 8.4% lower than one particle system, and the rotation decreases the midair colliding behaviors. A parametric scheme for drag coefficient of sand particle is summarized to modified the macroscopical Eulerian‐Lagrangian wind‐sand simulation, in which the saltation transport rate varies for different shapes of sand particles. This work indicts that an accurate prediction of shape and rotation effects is required to describe the sand movement and saltation transport.
Magnetic Field Risetimes of Negative Lightning First Return Strokes Over Land and Ocean
Authors: Nag Amitabh , Cummins Kenneth L.
Published: November 2018

We examined risetimes for negative first strokes occurring over land (3,427 strokes) and ocean (4,302 strokes) in Florida reported by the U.S. National Lightning Detection Network. The waveform characteristics were measured by a single National Lightning Detection Network sensor located less than 2 km from the coastline in Florida. All risetime measurements (10–50, 50–90, 10–90%, and threshold to peak) over both land and ocean exhibited statistically significant positive correlation with estimated peak current, but with small correlation coefficients. For a subset of 1,247 strokes selected to mitigate bias in our data, the median 10–50% magnetic field risetime was found to be 11% longer and the proportion of strokes having 10–50% risetimes in the range of 2.6 to 4.8 μs was 42% larger over ocean. We speculate that the slow‐front portion of radiation field waveforms for negative first strokes is affected by differences in surface properties over land versus over ocean that impact upward leader initiation.
Utilizing SMAP Soil Moisture Data to Constrain Irrigation in the Community Land Model
Authors: Felfelani Farshid , Pokhrel Yadu , Guan Kaiyu , Lawrence David M.
Published: November 2018

Irrigation representation in land surface models has been advanced over the past decade, but the soil moisture (SM) data from SMAP satellite have not yet been utilized in large‐scale irrigation modeling. Here we investigate the potential of improving irrigation representation in the Community Land Model version‐4.5 (CLM4.5) by assimilating SMAP data. Simulations are conducted over the heavily irrigated central U.S. region. We find that constraining the target SM in CLM4.5 using SMAP data assimilation with 1‐D Kalman filter reduces the root‐mean‐square error of simulated irrigation water requirement by 50% on average (for Nebraska, Kansas, and Texas) and significantly improves irrigation simulations by reducing the bias in irrigation water requirement by up to 60%. An a priori bias correction of SMAP data further improves these results in some regions but incrementally. Data assimilation also enhances SM simulations in CLM4.5. These results could provide a basis for improved modeling of irrigation and land‐atmosphere interactions.
The 2017 Record Marine Heatwave in the Southwestern Atlantic Shelf
Authors: Manta G. , de Mello S. , Trinchin R. , Badagian J. , Barreiro M.
Published: November 2018

Marine heatwaves (MHWs), considered as one when temperatures warmer than the 90th percentile based on a 30‐year historical baseline period are registered for five or more consecutive days, can have devastating ecosystem and socioeconomic consequences. MHWs were studied in the Southwestern Atlantic shelf (32–38°S) using daily sea surface temperatures between 1988 and 2017. More than half of the days with MHWs occurred since 2014. The most intense event happened in austral summer 2017, reaching temperatures of 26.8 °C, 1.7 °C above previous maximum. Regionally, an unprecedented combination of persistent extremely high air temperature and low wind speed probably led to an intense loop of heat gaining and stratification in the Rio de la Plata plume water's influence. At upper levels, the atmospheric circulation had a wavenumber of 3 pattern before the event and a blocking configuration during the event. Madden‐Julian Oscillation seems to have played a leading role in setting this planetary scale configuration.
The Role of Internal Variability in Twenty‐First‐Century Projections of the Seasonal Cycle of Northern Hemisphere Surface Temperature
Authors: Yettella Vineel , England Mark R.
Published: November 2018

The seasonal cycle is fundamental to the Earth's climate system, accounting for the vast majority of temperature variance. Understanding how the seasonal cycle will change in the future, and by when, is a key question with important implications. Here a 40‐member initial condition climate model ensemble is used to investigate the influence of internal variability on the detection of changes in the amplitude and timing of the seasonal cycle of surface temperature over Northern Hemisphere land in response to increasing greenhouse gases. Internal variability renders the detection of these changes challenging; even by the mid‐twenty‐first century, small ensembles will be insufficient to separate the forced signals from internal variability over many continental regions in the Northern Hemisphere. Despite this, projected changes over Europe, North Africa, and Siberia are large and easily detectable, even in a single member. Specifically, amplitude increases over Europe and North Africa while it decreases over Siberia. On the other hand, the timing of the seasonal cycle is delayed over all three regions. It is found that these changes are remarkably robust across model ensembles from the Coupled Model Intercomparison Project phase 5 archive. To understand the mechanisms underlying these robust changes, a simple energy balance model is used to partition changes into contributions arising from changes in the physical parameters that control the seasonal cycle. It is found that future changes in the seasonal cycle over the three regions are most strongly controlled by changes in surface longwave and turbulent heat fluxes.
The O(1S) 297.2‐nm Dayglow Emission: A Tracer of CO2 Density Variations in the Martian Lower Thermosphere
Authors: Gkouvelis L. , Gérard J.‐C. , Ritter B. , Hubert B. , Schneider N. M. , Jain S. K.
Published: November 2018

The O(1S) metastable atoms can radiatively relax by emitting airglow at 557.7 and 297.2 nm. The latter one has been observed with the Imaging Ultraviolet Spectrograph onboard the Mars Atmosphere and Volatile Evolution Mars orbiter since 2014. Limb profiles of the 297.2‐nm dayglow have been collected near periapsis with a spatial resolution of 5 km or less. They show a double‐peak structure that was previously predicted but never observed during earlier Mars missions. The production of both 297.2‐nm layers is dominated by photodissociation of CO2. Their altitude and brightness is variable with season and latitude, reflecting changes in the total column of CO2 present in the lower thermosphere. Since the lower emission peak near 85 km is solely produced by photodissociation, its peak is an indicator of the unit optical depth pressure level and the overlying CO2 column density. Its intensity is directly controlled by the Lyman‐α solar flux reaching the Martian upper atmosphere. We take advantage of the Lyman‐α flux measurements of the solar Extreme Ultraviolet Monitor instrument onboard Mars Atmosphere and Volatile Evolution to model the observed OI 297.2‐nm limb profiles. For this, we combine photodissociation sources with chemical processes and photoelectron impact excitation. To determine the relative importance of the excitation processes, we apply the model to the atmospheric structure measured by the Viking 1 lander before applying it to a model atmosphere. We find very good agreement with the lower peak structure and intensity if the CO2 density provided by the Mars Climate Database is scaled down by a factor between 0.50 and 0.66. We also determine that the previously uncertain quantum yield for production of O(1S) atoms by photodissociation of CO2 at Lyman‐α wavelength is about 8%.
Advances in the Eddy Covariance Approach to CH4 Monitoring Over Two and a Half Decades
Authors: Morin Timothy H.
Published: November 2018

Receding permafrost may expose the largest store of sequestered carbon to microbes ready to convert it to greenhouse gases. The fluxes of biogenic gases associated with boreal wetlands have historically been difficult to measure, limiting our understanding of what may happen as permafrost thaws. The many difficulties in working in high‐latitude climates have dramatically limited our understanding on the spatial and temporal distribution of fluxes and what is likely to change with a warming climate. The use of the eddy covariance approach to measure methane emissions has been developing steadily over the past 26 years. Taylor et al. (2018, https://doi.org/10.1029/2018JG004444) is an excellent example of the advancements made in the field. Here I summarize the history of the eddy covariance methane literature, describe advancements in spatial and temporal coverage, and look at important drivers of methane emissions.
miR-330-5p targets SPRY2 to promote hepatocellular carcinoma progression via MAPK/ERK signaling
Authors: Xiao Shuai , Yang Mengyuan , Yang Hao , Chang Ruimin , Fang Feng , Yang Lianyue
Published: November 2018

MicroRNAs (miRNAs) have been identified as critical modulators of cell proliferation and growth, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). Our previous miRNA microarray data have shown that miR-330-5p was always upregulated in HCC. However, the accurate role of miR-330-5p in HCC is still uncertain. Here, we report that miR-330-5p expression is upregulated in HCC tissues and cell lines, and is associated with tumor size, tumor nodule number, capsule formation and Tumor Node Metastasis (TNM) stage in HCC patients. Overexpression of miR-330-5p promotes proliferation and growth of HCC cells in vitro and in vivo, while miR-330-5p knockdown has the inverse effect. Moreover, using miRNA databases and dual luciferase report assay, we find miR-330-5p directly binds to the 3′-untranslated region (3′-UTR) of Sprouty2 (SPRY2). Then we find the novel biofunctional role of SPRY2 inactivation in promoting HCC progression. Finally, we confirm that miR-330-5p suppresses SPRY2 to promote proliferation via mitogen-activated protein kinases (MAPK)/extracellular regulated kinase (ERK) signaling in HCC. Taken together, our findings demonstrate the critical role of miR-330-5p in promoting HCC progression via targeting SPRY2 to activate MAPK/ERK signaling, which may provide a novel and promising prognostic marker and therapeutic target for HCC.
LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer
Authors: Gong Pihai , Qiao Fengchang , Wu Huazhang , Cui He , Li Yiping , Zheng Ying , Zhou Menghan , Fan Hong
Published: November 2018

Increasing studies showed that long-noncoding RNAs (lncRNAs) play important roles in the biological processes, including cancer initiation and progression. However, little is known about the exact role and regulation mechanism of lncRNA UCA1 during the progression of gastric cancer (GC). In this study, we found that UCA1 was aberrantly elevated in gastric cancer tissues, and was significantly associated with lymph node metastasis and TNM stage. In vivo and in vitro, enforced UCA1 level promoted cell migration and invasion of GC cell. Depleted UCA1 expression level attenuated the ability of cell migration and invasion in GC. And then, we detected that expression level of ZEB2, a transcription factor related to tumor metastasis, was regulated by UCA1 in GC cells. miR-203 targets and suppresses to ZEB2 expression. Furthermore, we found that UCA1 could directly interact with miR-203 and lead to the release of miR-203-targeted transcripts ZEB2. Herein, we revealed the novel mechanism of UCA1 on regulating metastasis-related gene by sponge regulatory axis during GC metastasis. Our findings indicated that UCA1 plays a critical role in metastatic GC by mediating sponge regulatory axis miR-203/ZEB2. To explore function of UCA1-miR-203-ZEB2 axis may provide an informative biomarker of malignancy and a highly selective anti-GC therapeutic target.
Seasonal energy exchange in sea ice retreat regions contributes to differences in projected Arctic warming
Authors: Boeke Robyn C. , Taylor Patrick C.
Published: November 2018

Rapid and, in many cases, unprecedented Arctic climate changes are having far-reaching impacts on natural and human systems. Despite state-of-the-art climate models capturing the rapid nature of Arctic climate change, termed Arctic amplification, they significantly disagree on its magnitude. Using a regional, process-oriented surface energy budget analysis, we argue that differences in seasonal energy exchanges in sea ice retreat regions via increased absorption and storage of sunlight in summer and increased upward surface turbulent fluxes in fall/winter contribute to the inter-model spread. Models able to more widely disperse energy drawn from the surface in sea ice retreat regions warm more, suggesting that differences in the local Arctic atmospheric circulation response contribute to the inter-model spread. We find that the principle mechanisms driving the inter-model spread in Arctic amplification operate locally on regional scales, requiring an improved understanding of atmosphere-ocean-sea ice interactions in sea ice retreat regions to reduce the spread.
Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants
Authors: Ogunshola Funsho , Anmole Gursev , Miller Rachel L. , Goering Emily , Nkosi Thandeka , Muema Daniel , Mann Jaclyn , Ismail Nasreen , Chopera Denis , Ndung’u Thumbi , Brockman Mark A. , Ndhlovu Zaza M
Published: November 2018

Some closely related human leukocyte antigen (HLA) alleles are associated with variable clinical outcomes following HIV-1 infection despite presenting the same viral epitopes. Mechanisms underlying these differences remain unclear but may be due to intrinsic characteristics of the HLA alleles or responding T cell repertoires. Here we examine CD8+T cell responses against the immunodominant HIV-1 Gag epitope TL9 (TPQDLNTML180–188) in the context of the protective allele B*81:01 and the less protective allele B*42:01. We observe a population of dual-reactive T cells that recognize TL9 presented by both B*81:01 and B*42:01 in individuals lacking one allele. The presence of dual-reactive T cells is associated with lower plasma viremia, suggesting a clinical benefit. In B*42:01 expressing individuals, the dual-reactive phenotype defines public T cell receptor (TCR) clones that recognize a wider range of TL9 escape variants, consistent with enhanced control of viral infection through containment of HIV-1 sequence adaptation.
A CRISPR–Cas9-triggered strand displacement amplification method for ultrasensitive DNA detection
Authors: Zhou Wenhua , Hu Li , Ying Liming , Zhao Zhen , Chu Paul K. , Yu Xue-Feng
Published: November 2018

Although polymerase chain reaction (PCR) is the most widely used method for DNA amplification, the requirement of thermocycling limits its non-laboratory applications. Isothermal DNA amplification techniques are hence valuable for on-site diagnostic applications in place of traditional PCR. Here we describe a true isothermal approach for amplifying and detecting double-stranded DNA based on a CRISPR–Cas9-triggered nicking endonuclease-mediated Strand Displacement Amplification method (namely CRISDA). CRISDA takes advantage of the high sensitivity/specificity and unique conformational rearrangements of CRISPR effectors in recognizing the target DNA. In combination with a peptide nucleic acid (PNA) invasion-mediated endpoint measurement, the method exhibits attomolar sensitivity and single-nucleotide specificity in detection of various DNA targets under a complex sample background. Additionally, by integrating the technique with a Cas9-mediated target enrichment approach, CRISDA exhibits sub-attomolar sensitivity. In summary, CRISDA is a powerful isothermal tool for ultrasensitive and specific detection of nucleic acids in point-of-care diagnostics and field analyses.
Slx5-Slx8 ubiquitin ligase targets active pools of the Yen1 nuclease to limit crossover formation
Authors: Talhaoui Ibtissam , Bernal Manuel , Mullen Janet R. , Dorison Hugo , Palancade Benoit , Brill Steven J. , Mazón Gerard
Published: November 2018

The repair of double-stranded DNA breaks (DSBs) by homologous recombination involves the formation of branched intermediates that can lead to crossovers following nucleolytic resolution. The nucleases Mus81-Mms4 and Yen1 are tightly controlled during the cell cycle to limit the extent of crossover formation and preserve genome integrity. Here we show that Yen1 is further regulated by sumoylation and ubiquitination. In vivo, Yen1 becomes sumoylated under conditions of DNA damage by the redundant activities of Siz1 and Siz2 SUMO ligases. Yen1 is also a substrate of the Slx5-Slx8 ubiquitin ligase. Loss of Slx5-Slx8 stabilizes the sumoylated fraction, attenuates Yen1 degradation at the G1/S transition, and results in persistent localization of Yen1 in nuclear foci. Slx5-Slx8-dependent ubiquitination of Yen1 occurs mainly at K714 and mutation of this lysine increases crossover formation during DSB repair and suppresses chromosome segregation defects in a mus81∆ background.
Colossal tunability in high frequency magnetoelectric voltage tunable inductors
Authors: Yan Yongke , Geng Liwei D. , Tan Yaohua , Ma Jianhua , Zhang Lujie , Sanghadasa Mohan , Ngo Khai , Ghosh Avik W. , Wang Yu U. , Priya Shashank
Published: November 2018

The electrical modulation of magnetization through the magnetoelectric effect provides a great opportunity for developing a new generation of tunable electrical components. Magnetoelectric voltage tunable inductors (VTIs) are designed to maximize the electric field control of permeability. In order to meet the need for power electronics, VTIs operating at high frequency with large tunability and low loss are required. Here we demonstrate magnetoelectric VTIs that exhibit remarkable high inductance tunability of over 750% up to 10 MHz, completely covering the frequency range of state-of-the-art power electronics. This breakthrough is achieved based on a concept of magnetocrystalline anisotropy (MCA) cancellation, predicted in a solid solution of nickel ferrite and cobalt ferrite through first-principles calculations. Phase field model simulations are employed to observe the domain-level strain-mediated coupling between magnetization and polarization. The model reveals small MCA facilitates the magnetic domain rotation, resulting in larger permeability sensitivity and inductance tunability.
Efficient solar-driven electrocatalytic CO2 reduction in a redox-medium-assisted system
Authors: Wang Yuhang , Liu Junlang , Wang Yifei , Wang Yonggang , Zheng Gengfeng
Published: November 2018

Solar-driven electrochemical carbon dioxide (CO2) reduction is capable of producing value-added chemicals and represents a potential route to alleviate carbon footprint in the global environment. However, the ever-changing sunlight illumination presents a substantial impediment of maintaining high electrocatalytic efficiency and stability for practical applications. Inspired by green plant photosynthesis with separate light reaction and (dark) carbon fixation steps, herein, we developed a redox-medium-assisted system that proceeds water oxidation with a nickel-iron hydroxide electrode under light illumination and stores the reduction energy using a zinc/zincate redox, which can be controllably released to spontaneously reduce CO2 into carbon monoxide (CO) with a gold nanocatalyst in dark condition. This redox-medium-assisted system enables a record-high solar-to-CO photoconversion efficiency of 15.6% under 1-sun intensity, and an outstanding electric energy efficiency of 63%. Furthermore, it allows a unique tuning capability of the solar-to-CO efficiency and selectivity by the current density applied during the carbon fixation.
MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size
Authors: Lewis Tommy L. , Kwon Seok-Kyu , Lee Annie , Shaw Reuben , Polleux Franck
Published: November 2018

Neurons display extreme degrees of polarization, including compartment-specific organelle morphology. In cortical, long-range projecting, pyramidal neurons (PNs), dendritic mitochondria are long and tubular whereas axonal mitochondria display uniformly short length. Here we explored the functional significance of maintaining small mitochondria for axonal development in vitro and in vivo. We report that the Drp1 ‘receptor’ Mitochondrial fission factor (MFF) is required for determining the size of mitochondria entering the axon and then for maintenance of their size along the distal portions of the axon without affecting their trafficking properties, presynaptic capture, membrane potential or ability to generate ATP. Strikingly, this increase in presynaptic mitochondrial size upon MFF downregulation augments their capacity for Ca2+ ([Ca2+]m) uptake during neurotransmission, leading to reduced presynaptic [Ca2+]c accumulation, decreased presynaptic release and terminal axon branching. Our results uncover a novel mechanism controlling neurotransmitter release and axon branching through fission-dependent regulation of presynaptic mitochondrial size.
Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection
Authors: Ramani Sasirekha , Stewart Christopher J. , Laucirica Daniel R. , Ajami Nadim J. , Robertson Bianca , Autran Chloe A. , Shinge Dhairyasheel , Rani Sandya , Anandan Sasirekha , Hu Liya , Ferreon Josephine C. , Kuruvilla Kurien A. , Petrosino Joseph F. , Venkataram Prasad B. V. , Bode Lars , Kang Gagandeep , Estes Mary K.
Published: November 2018

Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2’-fucosyllactose (2’FL), and 6’-siallylactose (6’SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance ofEnterobacter/Klebsiellain maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.
Spin decoherence in a two-qubit CPHASE gate: the critical role of tunneling noise
Authors: Huang Peihao , Zimmerman Neil M. , Bryant Garnett W.
Published: November 2018

Rapid progress in semiconductor spin qubits has enabled experimental demonstrations of a two-qubit logic gate. Understanding spin decoherence in a two-qubit logic gate is necessary for optimal qubit operation. We study spin decoherence due to 1/f charge noise for two electrons in a double quantum dot used for a two-qubit controlled-phase gate. In contrast to the usual belief, spin decoherence can be dominated by the tunneling noise from 1/f charge noise instead of the detuning noise. Tunneling noise can dominate because the effect of tunneling noise on the spin qubit is first order in the charge admixture; while the effect of the detuning noise is only second order. The different orders of contributions result in different detuning dependence of the decoherence, which provides a way to identify the noise source. We find that decoherence in a recent two-qubit experiment was dominated by the tunneling noise from 1/f charge noise. The results illustrate the importance of considering tunneling noise to design optimal operation of spin qubits.
Pre-clinical evaluation of a P. berghei-based whole-sporozoite malaria vaccine candidate
Authors: Mendes António M. , Reuling Isaie J. , Andrade Carolina M. , Otto Thomas D. , Machado Marta , Teixeira Filipa , Pissarra Joana , Gonçalves-Rosa Nataniel , Bonaparte Dolores , Sinfrónio João , Sanders Mandy , Janse Chris J. , Khan Shahid M. , Newbold Chris I. , Berriman Matthew , Lee Cynthia K. , Wu Yimin , Ockenhouse Christian F. , Sauerwein Robert W. , Prudêncio Miguel
Published: November 2018

Whole-sporozoite vaccination/immunization induces high levels of protective immunity in both rodent models of malaria and in humans. Recently, we generated a transgenic line of the rodent malaria parasiteP. berghei(Pb) that expresses theP. falciparum(Pf) circumsporozoite protein (PfCS), and showed that this parasite line (PbVac) was capable of (1) infecting and developing in human hepatocytes but not in human erythrocytes, and (2) inducing neutralizing antibodies against the humanPfparasite. Here, we analyzedPbVac in detail and developed tools necessary for its use in clinical studies. A microbiological contaminant-free Master Cell Bank ofPbVac parasites was generated through a process of cyclic propagation and clonal expansion in mice and mosquitoes and was genetically characterized. A highly sensitive qRT-PCR-based method was established that enablesPbVac parasite detection and quantification at low parasite densities in vivo. This method was employed in a biodistribution study in a rabbit model, revealing that the parasite is only present at the site of administration and in the liver up to 48 h post infection and is no longer detectable at any site 10 days after administration. An extensive toxicology investigation carried out in rabbits further showed the absence ofPbVac-related toxicity. In vivo drug sensitivity assays employing rodent models of infection showed that both the liver and the blood stage forms ofPbVac were completely eliminated by Malarone®treatment. Collectively, our pre-clinical safety assessment demonstrates thatPbVac possesses all characteristics necessary to advance into clinical evaluation.
Multiple physical aspects during the flow and heat transfer analysis of Carreau fluid with nanoparticles
Authors: Hashim  , Hafeez Abdul , Alshomrani Ali Saleh , Khan Masood
Published: November 2018

The current work is concerned with the two-dimensional boundary layer flow of a non-Newtonian fluid in the presence of nanoparticles. The heat and mass transfer mechanism for Carreau nanofluid flow due to a radially stretching/shrinking sheet is further investigated in this article. The governing physical situation is modelled in the form of partial differential equations and are simplified to a system of non-linear ordinary differential equations by employing dimensionless variables. Numerical simulations for non-dimensional velocity, temperature and concentration fields has been performed with the assistance of built-in Matlab solver bvp4c routine. One significant computational outcome of this study is the existence of multiple numerical solutions for the flow fields. The impacts of various developing parameters, for instance, Weissenberg number, power-law index, shrinking parameter, suction parameter, Prandtl number, Schmidt number, Brownian motion and thermophoresis parameter on the velocity, temperature and nanoparticles concentration are visualized through tables and graphical experiment. The numerical results demonstrate that the rates of heat and mass transfer are raised by higher Weissenberg number for first solution and an inverse is seen for second solution. Moreover, an increasing trend is seen in nanofluids temperature for both solutions with greater values of thermophoresis parameter. In addition, the numerical results obtained by the applied technique are validated with existing literature and found to be in an excellent agreement.
Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis
Authors: Katayama Shintaro , Ranga Vipin , Jouhilahti Eeva-Mari , Airenne Tomi T. , Johnson Mark S. , Mukherjee Krishanu , Bürglin Thomas R. , Kere Juha
Published: November 2018

Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is still subject to debate. We confirmed that human LEUTX acts as a TAATCC-targeting transcriptional activator, like other K50-type PAIRED-LIKE TFs. Phylogenetic comparisons revealed that Leutx proteins are conserved across Placentalia and comprise two conserved domains, the homeodomain, and a Leutx-specific domain containing putative transcriptional activation motifs (9aaTAD). Examination of human genotype resources revealed 116 allelic variants in LEUTX. Twenty-four variants potentially affect function, but they occur only heterozygously at low frequency. One variant affects a DNA-specificity determining residue, mutationally reachable by a one-base transition. In vitro and in silico experiments showed that this LEUTX mutation (alanine to valine at position 54 in the homeodomain) results in a transactivational loss-of-function to a minimal TAATCC-containing promoter and a 36 bp motif enriched in genes involved in embryo genome activation. A compensatory change in residue 47 restores function. The results support the notion that human LEUTX functions as a transcriptional activator important for human embryogenesis.