1,446 research outputs found
Understanding the nature of "superhard graphite"
Numerous experiments showed that on cold compression graphite transforms into
a new superhard and transparent allotrope. Several structures with different
topologies have been proposed for this phase. While experimental data are
consistent with these models, the only way to solve this puzzle is to find
which structure is kinetically easiest to form. Using state-of-the-art
molecular-dynamics transition path sampling simulations, we investigate kinetic
pathways of the pressure-induced transformation of graphite to various
superhard candidate structures. Unlike hitherto applied methods for elucidating
nature of superhard graphite, transition path sampling realistically models
nucleation events necessary for physically meaningful transformation kinetics.
We demonstrate that nucleation mechanism and kinetics lead to -carbon as the
final product. -carbon, initially competitor to -carbon, is ruled out by
phase growth. Bct-C structure is not expected to be produced by cold
compression due to less probable nucleation and higher barrier of formation
Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition
The strong interest in graphene has motivated the scalable production of high
quality graphene and graphene devices. Since large-scale graphene films
synthesized to date are typically polycrystalline, it is important to
characterize and control grain boundaries, generally believed to degrade
graphene quality. Here we study single-crystal graphene grains synthesized by
ambient CVD on polycrystalline Cu, and show how individual boundaries between
coalescing grains affect graphene's electronic properties. The graphene grains
show no definite epitaxial relationship with the Cu substrate, and can cross Cu
grain boundaries. The edges of these grains are found to be predominantly
parallel to zigzag directions. We show that grain boundaries give a significant
Raman "D" peak, impede electrical transport, and induce prominent weak
localization indicative of intervalley scattering in graphene. Finally, we
demonstrate an approach using pre-patterned growth seeds to control graphene
nucleation, opening a route towards scalable fabrication of single-crystal
graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material
Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies
Effect of plant traits and substrate moisture on the thermal performance of different plant species in vertical greenery systems
This study evaluated the effects of plant traits and substrate moisture on the thermal performance of four herbs and four shrubs, which are the most commonly used species in vertical greenery systems (VGSs), in humid subtropical Hong Kong over a one-year period. The canopy temperature reduction on sunny days was significantly correlated with canopy coverage and leaf area index (LAI), but not with daily evapotranspiration (ET). This indicated that the shading effect of VGSs, which is related to canopy coverage and LAI, was more prominent than ET cooling. The lack of significant correlation between substrate moisture, ET and canopy temperature indicated that substrate moisture and ET did not significantly enhance the canopy cooling of VGSs. Substrate moisture notably cooled the substrate on sunny days, and warmed the substrate on rainy days, which significantly affected substrate thermal behavior, but had less effect on canopy air temperature. The use of VGSs with eight common plant species on building envelopes reduced steady-state heat conduction by 18.7–39.8%, with Ficus elastica (rubber fig) causing the greatest canopy cooling
Fingerprint-based Wi-Fi indoor localization using map and inertial sensors
It is a common understanding that the localization accuracy can be improved by indoor maps and inertial sensors. However, there is a lack of concrete and generic solutions that combine these two features together and practically demonstrate its validity. This article aims to provide such a solution based on the mainstream fingerprint-based indoor localization approach. First, we introduce the theorem called reference points placement, which gives a theoretical guide to place reference points. Second, we design a Wi-Fi signal propagation-based cluster algorithm to reduce the amount of computation. The paper gives a parameter called reliability to overcome the skewing of inertial sensors. Then we also present Kalman filter and Markov chain to predict the system status. The system is able to provide high-accuracy real-time tracking by integrating indoor map and inertial sensors with Wi-Fi signal strength. Finally, the proposed work is evaluated and compared with the previous Wi-Fi indoor localization systems. In addition, the effect of inertial sensors’ reliability is also discussed. Results are drawn from a campus office building which is about 80 m×140 m with 57 access points
Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis
Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research
Role of the Functional Toll-Like Receptor-9 Promoter Polymorphism (-1237T/C) in Increased Risk of End-Stage Renal Disease:A Case-Control Study
Inflammation induced by infectious and noninfectious triggers in the kidney may lead to end stage renal disease (ESRD). Toll-like receptor 9 (TLR-9) a receptor for CpG DNA is involved in activation of immune cells in renal disease and may contribute to chronic inflammatory disease progression through an interleukin-6 (IL-6) dependent pathway. Previous studies indicate that -1237T/C confers regulatory effects on TLR-9 transcription. To date the effect of TLR-9 polymorphisms on ESRD remains unknown. We performed a case-control study and genotyped 630 ESRD patients and 415 controls for -1237T/C, -1486T/C and 1635G/A by real-time PCR assays and assessed plasma concentration of IL-6 by ELISA. Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -1237T/C promoter polymorphism. A significant association between -1237T/C in TLR-9 and ESRD was identified. The TCA, TTA and CCA haplotype of TLR-9 were associated with ESRD. ESRD patients carrying -1237TC had a higher mean plasma IL-6 level when compared with -1237TT. The TLR-9 transcriptional activity of the variant -1237CC allele is higher than the -1237TT allele. The results indicate that in a Han Chinese population the presence of the C allele of -1237T/C in the TLR-9 gene increases susceptibility towards development of ESRD. In vitro studies demonstrate that -1237T/C may be involved in the development of ESRD through transcriptional modulation of TLR-9
The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε
Replication fork stalling and accumulation of single-stranded DNA trigger the S phase checkpoint, a signalling cascade that, in budding yeast, leads to the activation of the Rad53 kinase. Rad53 is essential in maintaining cell viability, but its targets of regulation are still partially unknown. Here we show that Rad53 drives the hyper-SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε, principally following replication forks stalling induced by nucleotide depletion. Pol2 is the main target of SUMOylation within the replisome and its modification requires the SUMO-ligase Mms21, a subunit of the Smc5/6 complex. Moreover, the Smc5/6 complex co-purifies with Pol ε, independently of other replisome components. Finally, we map Pol2 SUMOylation to a single site within the N-terminal catalytic domain and identify a SUMO-interacting motif at the C-terminus of Pol2. These data suggest that the S phase checkpoint regulate Pol ε during replication stress through Pol2 SUMOylation and SUMO-binding abilit
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