The recent surge in event-related fMRI studies of episodic memory has generated a wealth of information about the neural correlates of encoding and retrieval processes. However, interpretation of ...individual studies is hampered by methodological differences, and by the fact that sample sizes are typically small. We submitted results from studies of episodic memory in healthy young adults, published between 1998 and 2007, to a voxel-wise quantitative meta-analysis using activation likelihood estimation Laird, A. R., McMillan, K. M., Lancaster, J. L., Kochunov, P., Turkeltaub, P. E., & Pardo, J. V., et al. (2005). A comparison of label-based review and ALE meta-analysis in the stroop task. Human Brain Mapping, 25, 6–21. We conducted separate meta-analyses for four contrasts of interest: episodic encoding success as measured in the subsequent-memory paradigm (subsequent Hit vs. Miss), episodic retrieval success (Hit vs. Correct Rejection), objective recollection (e.g., Source Hit vs. Item Hit), and subjective recollection (e.g., Remember vs. Know). Concordance maps revealed significant cross-study overlap for each contrast. In each case, the left hemisphere showed greater concordance than the right hemisphere. Both encoding and retrieval success were associated with activation in medial-temporal, prefrontal, and parietal regions. Left ventrolateral prefrontal cortex (PFC) and medial-temporal regions were more strongly involved in encoding, whereas left superior parietal and dorsolateral and anterior PFC regions were more strongly involved in retrieval. Objective recollection was associated with activation in multiple PFC regions, as well as multiple posterior parietal and medial-temporal areas, but not hippocampus. Subjective recollection, in contrast, showed left hippocampal involvement. In summary, these results identify broadly consistent activation patterns associated with episodic encoding and retrieval, and subjective and objective recollection, but also subtle differences among these processes.
Abnormality in mitochondria has been suggested to be associated with development of allergic airway disorders. In this study, to evaluate the relationship between mitochondrial reactive oxygen ...species (ROS) and NLRP3 inflammasome activation in allergic asthma, we used a newly developed mitochondrial ROS inhibitor, NecroX-5. NecroX-5 reduced the increase of mitochondrial ROS generation in airway inflammatory cells, as well as bronchial epithelial cells, NLRP3 inflammasome activation, the nuclear translocation of nuclear factor-κB, increased expression of various inflammatory mediators and pathophysiological features of allergic asthma in mice. Finally, blockade of IL-1β substantially reduced airway inflammation and hyperresponsiveness in the asthmatic mice. These findings suggest that mitochondrial ROS have a critical role in the pathogenesis of allergic airway inflammation through the modulation of NLRP3 inflammasome activation, providing a novel role of airway epithelial cells expressing NLRP3 inflammasome as an immune responder.
High-pressure resonance Raman experiments were performed on linear carbon chains Cn confined in double-wall carbon nanotubes (Cn@DWCNT). Our results indicate that the frequency of the chain mode ...undergoes a non-linear decreasing as pressure increases, in agreement with previous studies of the behavior of carbon chains into multi-wall carbon nanotubes. After the pressure cycle, the Cn modes present an irreversible frequency downshift together with an irreversible upshift (downshift) of the RBM modes (G+ band) of the inner tube. These spectral changes are interpreted as evidence of cross-linking between the carbon chain and the wall of the inner tube. Density functional theory (DFT) calculations were performed in order to shed light on the interpretation of the experimental data. The theoretical calculations show a pressure-induced charge transfer from the nanotube to the carbon chain, thus resulting in an increasing of the C≡C bond length, and consequently, a softening frequency of the Cn Raman mode. Furthermore, an irreversible cross-linking between the tube and Cn is observed when the maximum applied pressure is higher than the pressure of radial tube collapse is predicted by modelling, thus supporting the experimental results.
We propose the unique structure of highly dispersible single-walled carbon nanotubes (SWCNTs) in various solvents and polymers using the ZnO nano particle template. Buckled nanospring-shaped carbon ...nanotubes (NS-CNTs) were synthesized by a chemical reaction of ZnO nanoparticles with acid-treated SWCNTs and then dissolving ZnO through chemical etching. The unique structure of distorted hexagonal NS-CNTs encircled around ZnO nanoparticles was formed by the bending of SWCNTs caused by the agglomeration of chemically adsorbed Zn(OH)
, which is further crystallized as the polycrystalline ZnO inner core. The highly dispersible NS-CNTs could be incorporated in the poly(vinylidenefluoride-co-trifluoroethylene P(VDF-TrFE) copolymer, one of widely studied ferro- and piezo-electric polymer, up to the value of 15 wt% as nanofillers. The relative dielectric constant (K) of polymer nanocomposite, at 1 kHz, was greatly enhanced from 12.7 to the value of 62.5 at 11 wt% of NS-CNTs, corresponding to a 492% increase compared to that of pristine P(VDF-TrFE) with only a small dielectric loss tangent (D) of 0.1.
In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified ...exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23–41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 95% confidence interval (CI): 0.57, 0.77. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival 0.63 (95% CI: 0.45, 0.89) and newly collected samples 0.53 (95% CI: 0.38, 0.72). In patients with TPS ≥1%, PFS HRs were similar across archival 0.82 (95% CI: 0.66, 1.02) and newly collected samples 0.83 (95% CI: 0.68, 1.02).
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
Summary
Ethiopia is an ecologically diverse country; the low altitude regions are hot and humid whereas the high altitude regions are cooler. In this study we analyzed the transcriptome response of ...high altitude (Addis Ababa) and low altitude (Awash) chickens to heat stress conditions that are prevalent in the low altitude regions. The chickens were free ranged for 20 h in an enclosure in Awash, and then the heart, breast muscle and spleen tissues were collected at 6:00 am, 12:00 noon and 6:00 pm to follow a daily circadian cycle. Through RNA‐sequencing analysis, we identified differentially expressed genes (DEGs) that were significant (q < 0.05). These DEGs were subjected to protein–protein interaction (PPI) network and gene co‐expression network (GCN) analyses to understand their role. KEGG pathway analysis and Gene Ontology analysis of all the identified DEGs and the genes identified from the PPI network and GCN analyses revealed that several immune‐related pathways, such as proteasome, focal adhesion, influenza A, the ErbB signaling pathway and glycerophospholipid metabolism, were enriched in response to heat stress. These results suggest that the high altitude chickens were under heat stress and might be immunologically susceptible. Our findings will help in developing a genetic approach to mitigate production loss due to heat stress.
Abstract
Pressure plays a key role in the study of quantum materials. Its application in angle resolved photoemission (ARPES) studies, however, has so far been limited. Here, we report the evolution ...of the
k
-space electronic structure of bulk Ca
2
RuO
4
, lightly doped with Pr, under uniaxial strain. Using ultrathin plate-like crystals, we achieve uniaxial strain levels up to −4.1%, sufficient to suppress the insulating Mott phase and access the previously unexplored electronic structure of the metallic state at low temperature. ARPES experiments performed while tuning the uniaxial strain reveal that metallicity emerges from a marked redistribution of charge within the Ru
t
2
g
shell, accompanied by a sudden collapse of the spectral weight in the lower Hubbard band and the emergence of a well-defined Fermi surface which is devoid of pseudogaps. Our results highlight the profound roles of lattice energetics and of the multiorbital nature of Ca
2
RuO
4
in this archetypal Mott transition and open new perspectives for spectroscopic measurements.
AMoRE is an international project to search for the neutrinoless double beta decay of
100
Mo
using a detection technology consisting of magnetic microcalorimeters (MMCs) and molybdenum-based ...scintillating crystals. Data collection has begun for the current AMORE-I phase of the project, an upgrade from the previous pilot phase. AMoRE-I employs thirteen
48
depl
.
Ca
100
MoO
4
crystals and five
Li
2
100
MoO
4
crystals for a total crystal mass of 6.2 kg. Each detector module contains a scintillating crystal with two MMC channels for heat and light detection. We report the present status of the experiment and the performance of the detector modules.
Cyclostationary empirical orthogonal functions, derived from satellite altimetry, are combined with historical sea level measurements from tide gauges to reconstruct sea level fields from 1950 ...through 2009. Previous sea level reconstructions have utilized empirical orthogonal functions as basis functions, but by using cyclostationary empirical orthogonal functions and by addressing other aspects of the reconstruction procedure, an alternative sea level reconstruction can be computed. The procedure introduced here is capable of capturing the annual cycle and El Niño–Southern Oscillation (ENSO) signals back to 1950, with correlations between the reconstructed ENSO signal and common ENSO indices found to be over 0.9. The regional trends computed from the new reconstruction show good agreement with the trends obtained from the satellite altimetry, but some discrepancies are seen when comparing with previous sea level reconstructions over longer time periods. The computed rate of global mean sea level rise from the reconstructed time series is 1.97 mm/yr from 1950 to 2009 and 3.22 mm/yr from 1993 to 2009.
Key Points
A new sea level reconstruction has been developed using CSEOFs
CSEOFs allow for improved reconstruction of large‐scale signals like ENSO
Regional trend estimates differ from previous reconstructions
Abstract While intraventricular administration of epidermal growth factor (EGF) expands the proliferation of neural stem/progenitor cells in the subventricular zone (SVZ), overexpression of ...brain-derived neurotrophic factor (BDNF) is particularly effective in enhancing striatal neurogenesis. We assessed the induction of striatal neurogenesis and consequent functional recovery after chronic infusion of BDNF and EGF in an adult animal model of neonatal hypoxic-ischemic (HI) brain injury. Permanent brain damage was induced in CD-1® (ICR) mice (P7) by applying the ligation of unilateral carotid artery and hypoxic condition. At 6 weeks of age, the mice were randomly assigned to groups receiving a continuous 2-week infusion of one of the following treatments into the ventricle: BDNF, EGF, BDNF/EGF, or phosphate buffered saline (PBS). Two weeks after treatment, immunohistochemical analysis revealed an increase in the number of BrdU+ cells in the SVZ and striata of BDNF/EGF-treated mice. The number of new neurons co-stained with BrdU and βIII-tubulin was also significantly increased in the neostriata of BDNF/EGF-treated mice, compared with PBS group. In addition, the newly generated cells were expressed as migrating neuroblasts labeled with PSA-NCAM or doublecortin in the SVZ and the ventricular side of neostriata. The new striatal neurons were also differentiated as mature neurons co-labeled with BrdU+ /NeuN+ . When evaluated post-surgical 8 weeks, BDNF/EGF-treated mice exhibited significantly longer rotarod latencies at constant speed (48 rpm) and under accelerating condition (4–80 rpm), relative to PBS and untreated controls. In the forelimb-use asymmetry test, BDNF/EGF-treated mice showed significant improvement in the use of the contralateral forelimb. In contrast, this BDNF/EGF-associated functional recovery was abolished in mice receiving a co-infusion of 2% cytosine-b- d -arabinofuranoside (Ara-C), a mitotic inhibitor. Induction of striatal neurogenesis by the intraventricular administration of BDNF and EGF promoted functional recovery in an adult animal model of neonatal HI brain injury. The effect of Ara-C to completely block functional recovery indicates that the effect may be the result of newly generated neurons. Therefore, this treatment may offer a promising strategy for the restoration of motor function for adults with cerebral palsy (CP).
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