bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic memory effect at room temperature in exchange coupled NiFe2O4-NiO nanogranular system
Authors: Tian Zhaoming , Xu Longmeng , Gao Yuxia , Yuan Songliu , Xia Zhengcai
Published: November 2017

Compared to the low temperature memory effect observed in magnetic nanoparticles (NPs), here we report a room temperature memory effect in a Ferrimagnetic (FiM)-Antiferromagnetic exchange coupled NiFe2O4-NiO nanogranular system, which is experimentally studied by different protocols of dc magnetization relaxation measurements below the blocking temperature TB = 345 K. The interfacial exchange coupling between the FiM NiFe2O4 clusters and the spin-glassy like phase is proposed to provide an additional anisotropic energy, leading to the enhancement of the magnetic memory effect up to room temperature. The observed memory effect is discussed based on the multiple distribution of energy barriers for both the FiM NPs and interfacial magnetic exchange anisotropy.
Structure, transition temperature, and magnetoresistance of titanium-doped lanthanum barium manganite epilayers onto STO 001 substrates
Authors: Galca Aurelian Catalin , Oumezzine Marwène , Leca Aurel , Chirila Cristina Florentina , Kuncser Victor , Kuncser Andrei , Ghica Corneliu , Pasuk Iuliana , Oumezzine Mohamed
Published: November 2017

We have developed a thin film structure with a maximum magnetoresistance effect (MRE) at room temperature, which is one of the operating requirements for many applications. It is shown that La0.67Ba0.33Ti0.02Mn0.98O3 epilayers obtained by pulsed laser deposition onto (001) SrTiO3 single crystal substrates exhibit the highest MRE, ΔR/R(H)≈150% or ΔR/R(0)≈60% under 5 T, at 300 K, a temperature near to the corresponding Curie temperature (TC). Both doping with a tiny amount of titanium and induced stress due to lattice mismatch between the thin film and the substrate contribute to a decrease in TC as compared to the pristine compound and therefore to the decrease in the temperature where the highest MRE is recorded.
Extinction cross-section cancellation of a cylindrical radiating active source near a rigid corner and acoustic invisibility
Authors: Mitri F. G.
Published: November 2017

Active cloaking in its basic form requires that the extinction cross-section (or energy efficiency) from a radiating body vanishes. In this analysis, this physical effect is demonstrated for an active cylindrically radiating acoustic source in a non-viscous fluid, undergoing periodic axisymmetric harmonic vibrations near a rigid corner (i.e., quarter-space). The rigorous multipole expansion method in cylindrical coordinates, the method of images, and the addition theorem of cylindrical wave functions are used to derive closed-form mathematical expressions for the radiating, amplification, and extinction cross-sections of the active source. Numerical computations are performed assuming monopole and dipole modal oscillations of the circular source. The results reveal some of the situations where the extinction energy efficiency factor of the active source vanishes depending on its size and location with respect to the rigid corner, thus, achieving total invisibility. Moreover, the extinction energy efficiency factor varies between positive or negative values. These effects also occur for higher-order modal oscillations of the active source. The results find potential applications in the development of acoustic cloaking devices and invisibility in underwater acoustics or other areas.
Plasmon-enhanced optical nonlinearity for femtosecond all-optical switching
Authors: Wang Kuidong , Chen Long , Zhang Haijuan , Hsiao Hui-Hsin , Tsai Din Ping , Chen Jie
Published: November 2017

Ultrafast all-optical switching in metals can be an efficient way for high-speed active photonic devices. However, with the improvement in modulation speed, typically by reducing the optical switching pulse width from picoseconds to femtoseconds, the nonlinear optical response of the metal will decrease significantly, which hinders the realization of the sufficient modulation depth at femtosecond optical control. Here, by combining two optical nonlinear enhancement effects of surface plasmon polaritons, including their extreme sensitivity to refractive index change and their capability to induce strong localized optical fields, we have achieved an ∼50-times enhancement in the modulation depth simultaneously with a switching time of ∼75-fs. Such enhancement was found to be independent of the control intensity, which sets a basis for the future application of femtosecond switching at a minimum power.
Effective suppression of parametric instabilities with decoupled broadband lasers in plasma
Authors: Zhao Yao , Weng Suming , Chen Min , Zheng Jun , Zhuo Hongbin , Ren Chuang , Sheng Zhengming , Zhang Jie
Published: November 2017

A theoretical analysis for the stimulated Raman scattering (SRS) instability driven by two laser beams with a certain frequency difference is presented. It is found that strong coupling and enhanced SRS take place only when the unstable regions corresponding to the two beams are overlapped in the wavenumber space. Hence, a threshold of the beam frequency difference for their decoupling is found as a function of their intensity and plasma density. Based upon this, a strategy to suppress the SRS instability with decoupled broadband lasers (DBLs) is proposed. A DBL can be composed of tens or even hundreds of beamlets, where the beamlets are distributed uniformly in a broad spectrum range such as over 10% of the central frequency. Decoupling among the beamlets is found due to the limited beamlet energy and suitable frequency difference between neighboring beamlets. Particle-in-cell simulations demonstrate that SRS can be almost completely suppressed with DBLs at the laser intensity of ∼1015 W/cm2. Moreover, stimulated Brillouin scattering (SBS) will be suppressed simultaneously with DBLs as long as SRS is suppressed. DBLs can be attractive for driving inertial confined fusion.
On the light-induced enhancement in photovoltaic performance of PEDOT:PSS/Si organic-inorganic hybrid solar cells
Authors: Chen Jianhui , Yang Linlin , Ge Kunpeng , Chen Bingbing , Shen Yanjiao , Guo Jianxin , Liu Haixu , Xu Ying , Fan Jiandong , Mai Yaohua
Published: November 2017

Light-induced degradation has been identified to be a critical issue for most silicon-based solar cell technologies. This study presents an observation of an opposite light-induced enhancement (LIE) effect in photovoltaic performance in poly(3,4-ethylthiophene):polystyrenesulfonate/n-Si organic-inorganic hybrid solar cells. The reduced density of interface states under light soaking (LS) is found to be responsible for the LIE of the hybrid solar cells. An increased minor carrier lifetime under LS and a switchable photoluminescence intensity while applying a voltage bias are observed, providing evidence for the underlying physical mechanism.
Drawing organic photovoltaics using paint marker pens
Authors: Suzuki Kaori , Izawa Seiichiro , Chen Yujiao , Nakano Kyohei , Tajima Keisuke
Published: November 2017

Active layers for organic photovoltaic devices (OPVs) were prepared by hand drawing with paint marker pens containing solutions of the materials. Although the pen-coated organic films were visually non-uniform with quite high surface roughness, OPV devices using these films exhibited similar or slightly better performances than those using spin-coated films. As such, the pen-coating technique represents an easily accessible, inexpensive, and highly material-efficient method for fabricating OPVs.
A versatile apparatus for two-dimensional atomtronic quantum simulation
Authors: Haase T. A. , White D. H. , Brown D. J. , Herrera I. , Hoogerland M. D.
Published: November 2017

We report on the implementation of a novel optical setup for generating high-resolution customizable potentials to address ultracold bosonic atoms in two dimensions. Two key features are developed for this purpose. The customizable potential is produced with a direct image of a spatial light modulator, conducted with an in-vacuum imaging system of high numerical aperture. Custom potentials are drawn over an area of 600×400 μm with a resolution of 0.9 μm. The second development is a two-dimensional planar trap for atoms with an aspect ratio of 900 and spatial extent of Rayleigh range 1.6 × 1.6 mm, providing near-ballistic in-planar movement. We characterize the setup and present a brief catalog of experiments to highlight the versatility of the system.
Impact of livestock Scale on Rice Production in Battambang of Cambodia
Authors: Siek D , Xu S W , Wyu  , Ahmed A-G
Published: November 2017

Increasing the awareness of environmental protection especially in the rural regions is important as most the farmers reside in that region. Crop-livestock proudciton has proven in many ways to encourage environmental protection. This study analyzes among other factors the impacto of livestock scale on rice production. Two regressions: Ordinary Least Square (OLS) and stepwise regression was applied to investigate these interrelationship. The result stress of three factors encouraging livestock production namely size of farmland, scale of livestock and income acquired from other jobs. The study further provides recommends to the government based on the findings of the study.
Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute Salt Loading
Authors: Liu Kuo , Liu Zheng , Qi Han , Liu Bin , Wu Jingjing , Liu Yezhou , Zhang Jie , Cao Han , Yan Yuxiang , He Yan , Zhang Ling
Published: November 2017

BACKGROUND

Salt sensitivity of blood pressure (SSBP) increases the risk of cardiovascular complications, and the heritability of SSBP is about 50% in Chinese population. However, studies identifying genes involved in BP responses to acute sodium loading and diuresis shrinkage are still limited.

METHOD

A total of 342 essential hypertensives from Beijing were recruited in our study. A modified Sullivan’s acute oral saline load and diuresis shrinkage test was conducted to each individual. Medical history and lifestyle risk factors were obtained by questionnaire. Generalized linear model was used to examine the associations of 29 single-nucleotide polymorphisms (SNPs) with SSBP and false discovery rate (FDR) was used to correct P values for multiple testing.

RESULTS

In the process of acute sodium loading, after adjusting for age and 24-hour urinary sodium concentration, SNPs in CYP11B2, PRKG1, SLC8A1 genes were significantly associated with systolic BP (SBP) rising in the additive and recessive model; SNPs in CYP4A11, PRKG1, SLC8A1, and ADRB2 genes were significantly associated with diastolic BP (DBP) rising. In the process of diuresis shrinkage, SNPs of CLCNKA, eNOS, PRKG1 gene were associated with SBP and DBP decreasing. After FDR correction, rs434082 in SLC8A1 gene was still significantly associated with blood pressure rising during salt load. In the additive model, A allele increased DBP of 2.8 mm Hg (FDR_q = 0.029) and MAP of 3.1 mm Hg (FDR_q = 0.029) after adjusting for age and 24-hour urinary sodium concentration.

CONCLUSION

SLC8A1 gene may contribute to BP change in the process of acute sodium loading in a Han Chinese population.
The Impact of Intradialytic Pedaling Exercise on Arterial Stiffness: A Pilot Randomized Controlled Trial in a Hemodialysis Population
Authors: Cooke Alexandra B , Ta Vincent , Iqbal Sameena , Gomez Yessica-Haydee , Mavrakanas Thomas , Barré Paul , Vasilevsky Murray , Rahme Elham , Daskalopoulou Stella S
Published: November 2017

OBJECTIVES

Regular exercise is known to reduce arterial stiffness (AS) in hemodialysis patients. However, the impact of a more realistic intradialytic form of exercise, such as pedaling, is unclear. We aimed to examine (i) the effect of intradialytic pedaling exercise on AS over 4 months and (ii) the longer term effect of pedaling on AS 4 months after exercise cessation.

METHODS

Patients on stable in-center hemodialysis (3 x/week) were randomly assigned 1:1 to either intradialytic pedaling exercise (EX) or to a control group receiving usual hemodialysis (nonEX) for 4 months. At baseline and 4 months, peripheral and central blood pressure (BP) indices, heart rate (HR), augmentation index HR corrected (AIx75), and carotid-femoral pulse wave velocity (cfPWV) were assessed (applanation tonometry). Measurements were repeated in the EX group 4 months postexercise cessation.

RESULTS

As per protocol analysis was completed in 10 EX group participants (58 ± 17 years, body mass index 26 ± 4 kg/m2) and 10 nonEX group participants (53 ± 15 years, body mass index 27 ± 6 kg/m2). Peripheral and central BP was unchanged in both groups. AIx75 was unchanged in the EX group, however, a significant median increase of 3.5% [interquartile range, IQR 1.0, 8.5] was noted in the nonEX group (P = 0.009). We noted a significantly greater absolute decrease in cfPWV in the EX group compared to controls: −1.00 [IQR −1.95, 0.05] vs. 0.20 [IQR −0.10, 0.90] (P = 0.033). Interestingly, the decrease in cfPWV observed in the EX group was partially reversed 4 months after exercise cessation.

CONCLUSION

Intradialytic pedaling exercise has a beneficial impact on AS. This relationship warrants further investigation.

CLINICAL TRIALS REGISTRATION

Trial Number #NCT03027778 (clinicaltrials.gov)
TabPath: interactive tables for metabolic pathway analysis
Authors: Moraes Lauro Ângelo Gonçalves de , Felestrino Érica Barbosa , Assis Renata de Almeida Barbosa , Matos Diogo , Lima Joubert de Castro , Lima Leandro de Araújo , Almeida Nalvo Franco , Setubal João Carlos , Garcia Camila Carrião Machado , Moreira Leandro Marcio
Published: November 2017

Motivation

Information about metabolic pathways in a comparative context is one of the most powerful tool to help the understanding of genome-based differences in phenotypes among organisms. Although several platforms exist that provide a wealth of information on metabolic pathways of diverse organisms, the comparison among organisms using metabolic pathways is still a difficult task.

Results

We present TabPath (Tables for Metabolic Pathway), a web-based tool to facilitate comparison of metabolic pathways in genomes based on KEGG. From a selection of pathways and genomes of interest on the menu, TabPath generates user-friendly tables that facilitate analysis of variations in metabolism among the selected organisms.

Availability and implementation

TabPath is available at http://200.239.132.160:8686.
Human Cortical Thickness Organized into Genetically-determined Communities across Spatial Resolutions
Authors: Alexander-Bloch Aaron F , Mathias Samuel R , Fox Peter T , Olvera Rene L , Göring Harold H H , Duggirala Ravi , Curran Joanne E , Blangero John , Glahn David C
Published: November 2017

The cerebral cortex may be organized into anatomical genetic modules, communities of brain regions with shared genetic influences via pleiotropy. Such modules could represent novel phenotypes amenable to large-scale gene discovery. This modular structure was investigated with network analysis of in vivo MRI of extended pedigrees, revealing a “multiscale” structure where smaller and larger modules exist simultaneously and in partially overlapping fashion across spatial scales, in contrast to prior work suggesting a specific number of cortical thickness modules. Inter-regional genetic correlations, gene co-expression patterns and computational models indicate that two simple organizational principles account for a large proportion of the apparent complexity in the network of genetic correlations. First, regions are strongly genetically correlated with their homologs in the opposite cerebral hemisphere. Second, regions are strongly genetically correlated with nearby regions in the same hemisphere, with an initial steep decrease in genetic correlation with anatomical distance, followed by a more gradual decline. Understanding underlying organizational principles of genetic influence is a critical step towards a mechanistic model of how specific genes influence brain anatomy and mediate neuropsychiatric risk.
Gaussian approximation of general non-parametric posterior distributions
Authors: Shang Zuofeng , Cheng Guang
Published: November 2017

In a general class of Bayesian non-parametric models, we prove that the posterior distribution can be asymptotically approximated by a Gaussian process (GP). Our results apply to non-parametric exponential family that contains both Gaussian and non-Gaussian regression and also hold for both efficient (root-$n$) and inefficient (non-root-$n$) estimations. Our general approximation theorem does not rely on posterior conjugacy and can be verified in a class of GP priors that has a smoothing spline interpretation. In particular, the limiting posterior measure becomes prior free under a Bayesian version of ‘under-smoothing’ condition. Finally, we apply our approximation theorem to examine the asymptotic frequentist properties of Bayesian procedures such as credible regions and credible intervals.
Equivariant Morse Theory for the Norm-Square of a Moment Map on a Variety
Authors: Wilkin Graeme
Published: November 2017

We show that the main theorem of Morse theory holds for a large class of functions on singular spaces. The function must satisfy certain conditions extending the usual requirements on a manifold that Condition C holds and the gradient flow around the critical sets is well-behaved, and the singular space must satisfy a local deformation retract condition. We then show that these conditions are satisfied when the function is the norm-square of a moment map on an affine variety, and that the homotopy equivalence from this theorem is equivariant with respect to the associated Hamiltonian group action. An important special case of these results is that the main theorem of Morse theory holds for the norm square of a moment map on the space of representations of a finite quiver with relations.
Compliance with patient-reported outcome assessment in glioma patients: predictors for drop out
Authors: Renovanz Mirjam , Hechtner Marlene , Kohlmann Karoline , Janko Mareile , Nadji-Ohl Minou , Singer Susanne , Ringel Florian , Coburger Jan , Hickmann Anne-Katrin
Published: November 2017

Background

Patient-reported outcomes are of high importance in clinical neuro-oncology. However, assessment is still suboptimal. We aimed at exploring factors associated with the probability for a) drop out of study and b) death during follow-up.

Methods

Patients were assessed twice during follow-up visits scheduled within 3 to 5 months of each other by using 3 validated patient-reported outcome measures (t1: first assessment, t2: second assessment). As “death” was seen as a competing risk for drop out, univariate competing risk Cox regression models were applied to explore factors associated with dropping out (age, gender, WHO grade, living situation, recurrent surgery, Karnofsky Performance Status, time since diagnosis, and patient-reported outcomes assessed by Distress Thermometer, EORTC-QLQ-C30, EORTC-QLQ-BN20, and SCNS-SF-34G).

Results

Two hundred forty-six patients were eligible, 173 (70%) participated. Patients declining participation were diagnosed with glioblastomas more often than with other gliomas (56% vs 39%). At t2, 32 (18%) patients dropped out, n = 14 death-related, n = 18 for other reasons. Motor dysfunction (EORTC-QLQ-BN20) was associated with higher risk for non-death-related drop out (HR: 1.02; 95% CI, 1.00–1.03; P = .03). Death-related drop out was associated with age (HR: 1.09; 95% CI, 1.03–1.14; P = .002), Karnofsky Performance Status (HR: 0.92; 95% CI, 0.88–0.96; P < .001), lower physical functioning (EORTC-QLQ-C30; HR: 0.98; 95% CI, 0.96–1.00; P = .04) and lower motor functioning (EORTC-QLQ-BN20; HR: 1.020; 95% CI, 1.00–1.04; P = .02).

Conclusion

Patients with motor dysfunction and poorer clinical condition seem to be more likely to drop out of studies applying patient-reported outcome measures. This should be taken into account when planning studies assessing glioma patients and for interpretation of results of patient-reported outcome assessments in clinical routine.
Emergence of Resistance Mutations in Salmonella enterica Serovar Typhi Against Fluoroquinolones
Authors: Matono Takashi , Morita Masatomo , Yahara Koji , Lee Ken-ichi , Izumiya Hidemasa , Kaku Mitsuo , Ohnishi Makoto
Published: November 2017

Background

Little is known about the evolutionary process and emergence time of resistance mutations to fluoroquinolone in Salmonella enterica serovar Typhi.

Methods

We analyzed S. Typhi isolates collected from returned travelers between 2001 and 2016. Based on ciprofloxacin susceptibility, isolates were categorized as highly resistant (minimum inhibitory concentration [MIC] ≥ 4 μg/mL [CIPHR]), resistant (MIC = 1–2 μg/mL [CIPR]), intermediate susceptible (MIC = 0.12–0.5 μg/mL [CIPI]), and susceptible (MIC ≤ 0.06 μg/mL [CIPS]).

Results

A total of 107 isolates (33 CIPHR, 14 CIPR, 30 CIPI, and 30 CIPS) were analyzed by whole-genome sequencing; 2461 single nucleotide polymorphisms (SNPs) were identified. CIPS had no mutations in the gyrA or parC genes, while each CIPI had 1 of 3 single mutations in gyrA (encoding Ser83Phe [63.3%], Ser83Tyr [33.3%], or Asp87Asn [3.3%]). CIPHR had the same 3 mutations: 2 SNPs in gyrA (encoding Ser83Phe and Asp87Asn) and a third in parC (encoding Ser80Ile). CIPHR shared a common ancestor with CIPR and CIPI isolates harboring a single mutation in gyrA encoding Ser83Phe, suggesting that CIPHR emerged 16 to 23 years ago.

Conclusions

Three SNPs—2 in gyrA and 1 in parC—are present in S. Typhi strains highly resistant to fluoroquinolone, which were found to have evolved in 1993–2000, approximately 10 years after the beginning of the ciprofloxacin era. Highly resistant strains with survival advantages arose from strains harboring a single mutation in gyrA encoding Ser83Phe. Judicious use of fluoroquinolones is warranted to prevent acceleration of such resistance mechanisms in the future.
Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options
Authors: Meloni Seema T , Onwuamah Chika K , Agbaji Oche , Chaplin Beth , Olaleye David O , Audu Rosemary , Samuels Jay , Ezechi Oliver , Imade Godwin , Musa Adesola Z , Odaibo Georgina , Okpokwu Jonathan , Rawizza Holly , Mu’azu Muhammad A , Dalhatu Ibrahim , Ahmed Mukhtar , Okonkwo Prosper , Raizes Elliot , Ujah Innocent A O , Yang Chunfu , Idigbe Emmanuel O , Kanki Phyllis J
Published: November 2017

Background

Although there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring.

Methods

Paired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University’s HIVdb program.

Results

Sequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0–6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with >6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF.

Conclusions

In the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.
Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα
Authors: Krumm Elizabeth A , Patel Vipa J , Tillery Taylor S , Yasrebi Ali , Shen Jianliang , Guo Grace L , Marco Stephanie M , Buckley Brian T , Roepke Troy A
Published: November 2017

Flame retardants (FRs) such as polybrominated diphenyl ethers and organophosphate FR (OPFR) persist in the environment and interact with multiple nuclear receptors involved in homeostasis, including estrogen receptors (ERs). However, little is known about the effects of FR, especially OPFR, on mammalian neuroendocrine functions. Therefore, we investigated if exposure to FR alters hypothalamic gene expression and whole-animal physiology in adult wild-type (WT) and ERα KO mice. Intact WT and KO males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17α-ethynylestradiol (2.5 μg/kg), 2,2’, 4,4-tetrabromodiphenyl ether (BDE-47, 1 or 10 mg/kg), or an OPFR mixture {1 or 10 mg/kg of tris(1, 3-dichloro-2-propyl)phosphate, triphenyl phosphate, and tricresyl phosphate each} for 28 days. Body weight, food intake, body composition, glucose and insulin tolerance, plasma hormone levels, and hypothalamic and liver gene expression were measured. Expression of neuropeptides, receptors, and cation channels was differentially altered between WT males and females. OPFR suppressed body weight and energy intake in males. FR increased fasting glucose levels in males, and BDE-47 augmented glucose clearance in females. Liver gene expression indicated FXR activation by BDE-47 and PXR and CAR activation by OPFR. In males, OPFR increased ghrelin but decreased leptin and insulin independent of body weight. The loss of ERα reduced the effects of both FR on hypothalamic and liver gene expression and plasma hormone levels. The physiological implications are that males are more sensitive than ovariectomized females to OPFR exposure and that these effects are mediated, in part, by ERα.
Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy*
Authors: Frat Jean-Pierre , Ragot Stéphanie , Coudroy Rémi , Constantin Jean-Michel , Girault Christophe , Prat Gwénael , Boulain Thierry , Demoule Alexandre , Ricard Jean-Damien , Razazi Keyvan , Lascarrou Jean-Baptiste , Devaquet Jérôme , Mira Jean-Paul , Argaud Laurent , Chakarian Jean-Charles , Fartoukh Muriel , Nseir Saad , Mercat Alain , Brochard Laurent , Robert René , Thille Arnaud W.
Published: November 2017

Objectives:

In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques.

Design:

Post hoc analysis of a randomized clinical trial.

Setting:

Twenty-three ICUs.

Patients:

Patients with a respiratory rate greater than 25 breaths/min and a Pao
2/Fio
2 ratio less than or equal to 300 mm Hg.

Intervention:

Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation.

Measurement and Main Results:

Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13–6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a Pao
2/Fio
2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62–11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22–8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality.

Conclusions:

In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A Pao
2/Fio
2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation.
Finding domain-general metacognitive mechanisms requires using appropriate tasks
Authors: Ruby Eugene , Giles Nathan , Lau Hakwan
Published: November 2017

An important yet unresolved question is whether or not metacognition consists of domain-general or domain-specific mechanisms. While most studies on this topic suggest a dissociation between metacognitive abilities at the neural level, there are conflicting reports at the behavioral level. Specifically, while McCurdy et al. (2013) found a positive correlation between metacognitive efficiency for visual perception and memory, Baird et al. (2013) didn’t find this correlation. One possible explanation for this disparity is that the former included two-alternative-forced choice (2AFC) judgments in both their visual and memory tasks, whereas the latter used 2AFC for one task and yes/no (YN) judgments for the other. In support of this hypothesis, we ran two online experiments meant to mirror McCurdy et al. (2013) and Baird et al. (2013) with considerable statistical power (n=100), and replicated the main findings of both studies. This suggests the finding of McCurdy et al (2013) was not a ‘fluke’ (i.e. false positive). In a third experiment with the same sample size, which included YN judgments for both tasks, we did not find a correlation between metacognitive functions, suggesting that the conflict between McCurdy et al. (2013) and Baird et al. (2013) stemmed from the use of YN judgments in the latter study. Our results underscore the need to avoid conflating 2AFC and YN judgments, which is a common problem.
Axons from the Trigeminal Ganglia are the Earliest Afferent Projections to the Mouse Cerebellum
Authors: Marzban Hassan , Rahimi-Balaei Maryam , Hawkes Richard
Published: November 2017

The first stage standard model for the development of afferent pathways to the cerebellum is that ingrowing axons target the embryonic Purkinje cells (E13-E16 in mice). Perinatally and early postnatal (E18-P15) the climbing fibers translocate to the Purkinje cell dendrites, and as the granular layer develops the mossy fibers translocate from the Purkinje cell somata and synapse with granule cell dendrites. In this report we describe a novel earlier stage in the development. Immunostaining for a neurofilament-associated antigen (NAA) reveals the early axon distributions with remarkable clarity. Axons from the trigeminal system enter the cerebellar primordium as early as embryo age (E)9. By using a combination of axon tract tracing, analysis ofneurogenin1null mice – which do not develop trigeminal ganglia – and mouse embryos maintainedin vitro– we show that the first axons to innervate the cerebellar primordium are direct projections from the trigeminal ganglia. The data show that the early trigeminal projections arein situbefore the Purkinje cells are born, and double immunostaining for NAA and markers of the different domains in the cerebellar primordium reveal that they first target the cerebellar nuclear neurons of the nuclear transitory zone (E9-E10), and only later (E10-E11) extend collateral branches to the Purkinje cell plate.
Near-Atomic Cryo-EM Imaging of a Small Protein Displayed on a Designed Scaffolding System
Authors: Liu Yuxi , Gonen Shane , Gonen Tamir , Yeates Todd O.
Published: November 2017

Current single particle electron cryo-microscopy (cryo-EM) techniques can produce images of large protein assemblies and macromolecular complexes at atomic level detail without the need for crystal growth. However, proteins of smaller size, typical of those found throughout the cell, are not presently amenable to detailed structural elucidation by cryo-EM. Here we use protein design to create a modular, symmetrical scaffolding system to make protein molecules of typical size amenable to cryo-EM. Using a rigid continuous alpha-helical linker, we connect a small 17 kDa protein (DARPin) to a protein subunit that was designed to self-assemble into a cage with cubic symmetry. We show that the resulting construct is amenable to structural analysis by single particle cryo-EM, allowing us to identify and solve the structure of the attached small protein at near-atomic detail, ranging from 3.5 to 5 Å resolution. The result demonstrates that proteins considerably smaller than the theoretical limit of 50 kDa for cryo-EM can be visualized clearly when arrayed in a rigid fashion on a symmetric designed protein scaffold. Furthermore, because the amino acid sequence of a DARPin can be chosen to confer tight binding to various other protein or nucleic acid molecules, the system provides a future route for imaging diverse macromolecules, potentially broadening the application of cryoEM to proteins of typical size in the cell.

Significance statement

New electron microscopy methods are making it possible to view the structures of large proteins and nucleic acid complexes at atomic detail, but the methods are difficult to apply to molecules smaller than about 50 kDa, which is larger than the size of the average protein in the cell. The present work demonstrates that a protein much smaller than that limit can be successfully visualized when it is attached to a large protein scaffold designed to hold 12 copies of the attached protein in symmetric and rigidly defined orientations. The small protein chosen for attachment and visualization can be modified to bind to other diverse proteins, opening up a new avenue for imaging cellular proteins by cryo-EM.
Inferring the Evolutionary Reduction of Corm Lobation inIsoëtesusing Bayesian Model-Averaged Ancestral State Reconstruction
Authors: Freund Forrest D. , Freyman William A. , Rothfels Carl J.
Published: November 2017

Inferring the evolution of characters inIsoëteshas been problematic, as these plants are morphologically conservative and yet highly variable and homoplasious within that conserved base morphology. However, molecular phylogenies have given us a valuable tool to test hypothesis of character evolution within the genus. One such hypothesis is that extantIsoëteshave undergone a morphological reduction from larger arborescent lycophyte ancestors. In this work we examine the reduction in lobe numbers on the underground trunk, or corm, over evolutionary time. Using reversible-jump MCMC and Bayesian inference, our results support the hypothesis of a directional reduction in lobe number inIsoëtes, with the best-supported model of character evolution being one of irreversible reduction. Furthermore, the most probable ancestral corm lobe number of extantIsoëtesis three, and a reduction to two lobes has occurred at least six times. From our results, we can infer that corm lobation, like many other traits inIsoëtes, shows a degree of homoplasy, yet also shows ongoing evolutionary reduction.
An essential post-developmental role for Lis1 in mice
Authors: Hines Timothy J. , Gao Xu , Sahu Subhshri , Lange Meghann M. , Turner Jill R. , Twiss Jeffery L. , Smith Deanna S.
Published: November 2017

LIS1 mutations cause lissencephaly (LIS), a severe developmental brain malformation. Much less is known about its role in the mature nervous system. LIS1 regulates the microtubule motor cytoplasmic dynein 1 (dynein), and as LIS1 and dynein are both expressed in the adult nervous system, Lis1 could potentially regulate dynein-dependent processes such as axonal transport. We therefore knocked out Lis1 in adult mice using tamoxifen-induced, Cre-ER-mediated recombination. When an actin promoter was used to drive Cre-ER expression (Act-Cre-ER), heterozygous Lis1 KO caused no obvious change in viability or behavior, despite evidence of widespread recombination by a Cre reporter three weeks after tamoxifen exposure. In contrast, homozygous Lis1 KO caused the rapid onset of neurological symptoms in both male and female mice. One tamoxifen-dosing regimen caused prominent recombination in the midbrain/hindbrain, PNS, and cardiac/skeletal muscle within a week; these mice developed severe symptoms in that time frame and were euthanized. A different tamoxifen regimen resulted in delayed recombination in midbrain/hindbrain, but not in other tissues, and also delayed the onset of symptoms. This indicates that Lis1 loss in the midbrain/hindbrain causes the severe phenotype. In support of this, brainstem regions known to house cardiorespiratory centers showed signs of axonal dysfunction in KO animals. Transport defects, neurofilament alterations, and varicosities were observed in axons in cultured DRG neurons from KO animals. Because no symptoms were observed when a cardiac specific Cre-ER promoter was used, we propose a vital role for Lis1 in autonomic neurons and implicate defective axonal transport in the KO phenotype.

SIGNIFICANCE STATEMENT

Mammalian Lis1 is best known for its role in brain development. Lis1 binds to and regulates the microtubule motor, cytoplasmic dynein. We show that Lis1 function is needed post-developmentally and provide evidence that loss of Lis1 in the hindbrain leads to death. The effect is dose dependent in mice, as loss of only one allele does not produce an overt phenotype. However, since LIS1 haploinsufficiency causes lissencephaly (LIS) in humans, our study raises the possibility that post-developmental axonal transport defects could contribute to worsening symptoms in children with LIS1 mutations. Our data are consistent with the hypothesis is that Lis1 regulates dynein-dependent axon transport in the mature nervous system.
The Fluid Membrane determines Mechanics of Red Blood Cell Extracellular Vesicles and is Softened in Hereditary Spherocytosis
Authors: Vorselen Daan , Dommelen Susan M. van , Sorkin Raya , Schiller Jürgen , Wijk Richard van , Schiffelers Raymond M. , Wuite Gijs J.L. , Roos Wouter H.
Published: November 2017

Extracellular vesicles (EVs) are widely studied regarding their role in cell-to-cell communication and disease, as well as for applications as biomarker or drug delivery vehicle. EVs contain both membrane and intraluminal proteins, affecting their structural properties and thereby likely their functioning. Here, we use atomic force microscopy for the mechanical characterization of red blood cell (RBC) EVs from healthy individuals as well as from a patient with hereditary spherocytosis (HS) due to ankyrin deficiency. We show that the EVs are packed with proteins, yet their response to indentation is similar to that of a fluid lipid vesicle lacking proteins. The bending modulus of RBC EVs of healthy donors is ~15kbT, agreeing well with the bending modulus of the RBC membrane. Surprisingly, whereas RBCs become more rigid in HS, the excreted vesicles of a patient with this blood disorder have a significantly (~50%) lower bending modulus than donor EVs. These results shed new light on the mechanism and effects of EV budding and may underlie the reported increase in vesiculation and stiffening of RBCs in hereditary spherocytosis patients.
Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin/F-actin based oscillatory ratchet mechanism
Authors: Paatero Ilkka , Sauteur Loïc , Lee Minkyoung , Lagendijk Anne K. , Heutschi Daniel , Bieli Dimitri , Hogan Benjamin M. , Affolter Markus , Belting Heinz-Georg
Published: November 2017

Angiogenesis and vascular remodeling are driven by a wide range of endothelial cell behaviors, such as cell divisions, cell movements, cell shape and polarity changes. To decipher the cellular and molecular mechanism of cell movements, we have analyzed the dynamics of different junctional components during blood vessel anastomosis in vivo. We show that endothelial cell movements are associated with oscillating lamellipodia-like structures, which are orientated in the direction of these movements. These structures emerge from endothelial cell junctions and we thus call them junction-based lamellipodia (JBL). High-resolution time-lapse imaging shows that JBL are formed by F-actin based protrusions at the front end of moving cells. These protrusions also contain diffusely distributed VE-cadherin, whereas the junctional protein ZO-1 (Zona occludens 1) remains at the junction. Subsequently, a new junction is formed at the front of the JBL and the proximal junction is pulled towards the newly established distal junction. JBL function is highly dependent on F-actin dynamics. Inhibition of F-actin polymerization prevents JBL formation, whereas Rac-1 inhibition interferes with JBL oscillations. Both interventions disrupt endothelial junction formation and cell elongation. To examine the role of VE-cadherin (encoded by cdh5 gene) in this process, we generated a targeted mutation in VE-cadherin gene (cdh5ubs25), which prevents VE-cad/F-actin interaction. Although homozygous ve-cadherin mutants form JBL, these JBL are less dynamic and do not promote endothelial cell elongation. Taken together, our observations suggest a novel oscillating ratchet-like mechanism, which is used by endothelial cells to move along or over each other and thus provides the physical means for cell rearrangements.
IDENTIFICATION OF AN EARLY SUBSET OF CEREBELLAR NUCLEI NEURONS IN MICE
Authors: Rahimi-Balaei Maryam , Amiri Shayan , Lamonerie Thomas , Wu Sih-Rong , Zoghbi Huda Y. , Consalez G. Giacomo , Goldowitz Daniel , Marzban Hassan
Published: November 2017

Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium. Embryos were collected at early stages of development and processed for immunohistochemistry (IHC), Western blotting,in situhybridization (ISH), embryonic culture, DiI labeling, and flow cytometry analysis (FCM). Our findings indicate that a subset of CN neurons expressing α-synuclein (SNCA), OTX2, MEIS2, and p75NTR (NGFR) are located in the rostroventral region of the nuclear transitory zone (NTZ). While CN neurons derived from the rhombic lip are positioned in the caudodorsal area of the NTZ in the cerebellar primordium. Utilizing Otx2-GFP andAtoh1−/−mice, we have determined that these cells do not originate from the germinal zone of the cerebellar primordium. These results suggest the existence of a novel extrinsic germinal zone for the cerebellar primordium, possibly the mesencephalon, from which early CN neurons originate.

SIGNIFICANCE STATEMENT

The cerebellum contains a variety of distinct neuronal populations, each playing a significant role in its function within the brain. This research demonstrates that a particular subset of cerebellar nuclei neurons originates from a previously unrecognized germinal zone specific to the cerebellar primordium, independently of Atoh1’s influence.
Functional categories in macaque frontal eye field
Authors: Lowe Kaleb A. , Schall Jeffrey D.
Published: November 2017

Frontal eye field (FEF) in macaque monkeys contributes to visual attention, visual-motor transformations and production of eye movements. Traditionally, neurons in FEF have been classified by the magnitude of increased discharge rates following visual stimulus presentation, during a waiting period, and associated with eye movement production. However, considerable heterogeneity remains within the traditional visual, visuomovement and movement categories. Cluster analysis is a data-driven method of identifying self-segregating groups within a dataset. Because many cluster analysis techniques exist and cluster outcomes vary with analysis assumptions, consensus clustering aggregates over multiple cluster analyses, identifying robust groups. To describe more comprehensively the neuronal composition of FEF, we applied a consensus clustering technique for unsupervised categorization of patterns of spike rate modulation measured during a memory-guided saccade task. We report ten functional categories, expanding on the traditional three. Categories were distinguished by latency, magnitude, and sign of visual response, presence of sustained activity, and dynamics, magnitude and sign of saccade-related modulation. Consensus clustering can include other metrics and can be applied to datasets from other brain regions to provides better information guiding microcircuit models of cortical function.

SIGNIFICANCE STATEMENT

The contribution of a brain region cannot be understood without knowing the diversity, arrangement, and circuitry of constituent neurons. Traditional descriptions of frontal eye field include visual, visuo-saccadic, and saccadic categories. Here, we employ a novel consensus clustering method to identify more reliably functional categories in neural data. While confirming the traditional categories, consensus clustering distinguishes additional, previously unappreciated diversity in neural activity patterns. Such information is necessary to formulate correct microcircuit models of cortical function.
Membrane curvature and the Tol-Pal complex determine polar localization of the chemoreceptor Tar inE. coli
Authors: Saaki Terrens N. V. , Strahl Henrik , Hamoen Leendert W.
Published: November 2017

Chemoreceptors are localized at the cell poles ofEscherichia coliand other rod-shaped bacteria. Over the years different mechanisms have been put forward to explain this polar localization; from stochastic clustering, membrane curvature driven localization, interactions with the Tol-Pal complex, to nucleoid exclusion. To evaluate these mechanisms, we monitored the cellular localization of the aspartate chemoreceptor Tar in different deletion mutants. We did not find any indication for either stochastic cluster formation or nucleoid exclusion. However, the presence of a functional Tol-Pal complex appeared to be essential to retain Tar at cell poles. This finding also implies that the curvature of cell poles does not attract chemoreceptor complexes. Interestingly, Tar still accumulated at midcell intoland inpaldeletion mutants. In these mutants, the protein appears to gather at the base of division septa, a region characterised by strong membrane curvature. Chemoreceptors, like Tar, form trimer-of-dimers that bend the cell membrane due to a rigid tripod structure with an estimated curvature of approximately 37 nm. This curvature approaches the curvature of the cell membrane generated during cell division, and localization of chemoreceptor tripods at curved membrane areas is therefore energetically favourable as it lowers membrane tension. Indeed, when we introduced mutations in Tar that abolish the rigid tripod structure, the protein was no longer able to accumulate at midcell or cell poles. These findings favour a model where chemoreceptor localization inE. coliis driven by strong membrane curvature and association with the Tol-Pal complex.

Importance

Bacteria have exquisite mechanisms to sense and to adapt to the environment they live in. One such mechanism involves the chemotaxis signal transduction pathway, in which chemoreceptors specifically bind certain attracting or repelling molecules and transduce the signals to the cell. In different rod-shaped bacteria, these chemoreceptors localize specifically to cell poles. Here, we examined the polar localization of the aspartate chemoreceptor Tar inE. coli, and found that membrane curvature at cell division sites and interaction with the Tal-pol protein complex, localize Tar at cell division sites, the future cell poles. This study shows how membrane curvature can guide localization of proteins in a cell.