Molecular ordering and charge transport have been studied computationally for 22 conjugated oligomers fabricated as crystal or thin-film semiconductors. Molecular dynamics (MD) simulations are ...employed to equilibrate crystal morphologies at 300 K. The paracrystalline order parameter, g, is calculated to characterize structural order in the materials. Charge-transport dynamics are predicted using kinetic Monte Carlo methods based on a charge-hopping mechanism described by the Marcus theory of electron transfer to calculate charge-transfer rates using the VOTCA package. We introduce an error function to assess the reliability of our computed values to reproduce experimental hole mobilities in both crystalline and thin-film morphologies of the 22 conjugated oligomers. For each of the oligomers, we compute hole mobility with three different theoretical models incorporating increasing measures of disorder: (1) a perfect crystal, based on the experimentally derived crystal structure, with no disorder, (2) an MD-equilibrated structure incorporating thermal disorder into the crystal structure, and (3) model 2 above but also incorporating energetic disorder arising from variations in site energies. For the series of known crystals with long-range order, we find that the perfect crystal model produces hole mobilities giving the best fit to experimental data. For the series of thin-film morphologies with short-range order, we observe that the presence of both thermal and energetic disorder is essential for accurate calculation. We also discuss the interplay between hole mobility and other charge-transport parameters in these morphologies, such as reorganization energy and energetic disorder.
The unique optical properties of metals are at the core of many areas of research and applications, including plasmonics, metamaterials, superlensing and subdiffraction focusing, optical antennas and ...surface enhanced Raman scattering. One important length scale inherent in metamaterials and plasmonics research activities in the microwave, terahertz, infrared, visible and ultraviolet ranges is the skin depth of metal, which remains at the submicrometre level throughout the broad spectral range. One prominent question is whether terahertz electromagnetic waves can be controlled on the nanoscale to achieve new functionalities in the sub-skin-depth regime. Here, we show that a λ/30,000 slit on metal film acts as a nanogap-capacitor charged by light-induced currents, enhancing the electric field by orders of magnitudes.
Summary
Neuromuscular electrical stimulation (NMES) has been used as a therapeutic intervention for dysphagia. However, the therapeutic effects of NMES lack supporting evidence. In recent years, NMES ...combined with traditional swallowing therapy has been used to improve functional recovery in patients with post‐stroke dysphagia. This study aimed to investigate the effects of effortful swallowing combined with neuromuscular electrical stimulation on hyoid bone movement and swallowing function in stroke patients. Fifty stroke patients with mild dysphagia who were able to swallow against the resistance applied by using NMES and cooperate actively in training were included. This study was designed as a 6‐week single‐blind, randomised, controlled study. In the experimental group, two pairs of electrodes were placed horizontally in the infrahyoid region to depress the hyoid bone. The NMES intensity was increased gradually until the participants felt a grabbing sensation in their neck and performed an effortful swallow during the stimulation. In the placebo group, the same procedure was followed except for the intensity, which was increased gradually until the participants felt an electrical sensation. All participants underwent this intervention for 30 min per session, 5 sessions per week, for 6 weeks. Videofluoroscopic swallowing studies (VFSS) were carried out before and after the intervention and kinematics of the hyoid bone and swallowing function were analysed based on the VFSS. The experimental group revealed a significant increase in anterior and superior hyoid bone movement and the pharyngeal phase of the swallowing function. This intervention can be used as a novel remedial approach in dysphagic stroke patients.
To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics.
We prospectively evaluated the ...efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples.
Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P=0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P=0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications.
The present study showed that HER2+GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production ...and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.
Cheddar-type cheese was fortified with the antioxidant Inula britannica flower extract (IBE). Cheddar-type cheeses manufactured with varying concentrations of IBE (0, 0.25, 0.5, 0.75, and 1% wt/vol) ...were analyzed during storage at 4°C, 0, 1, 2, and 3 wk after production. Higher IBE concentrations resulted in higher protein and ash contents, with a concomitant decrease in pH, total solid, and fat content relative to the unfortified control cheese. The total phenolic content also increased with IBE concentration, but decreased over longer storage periods. The antioxidant activities of the cheeses, determined as 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity and ferric thiocyanate assay results, increased proportionally to the total phenolic content. The highest antioxidant effect was observed in the 1% IBE-fortified cheese, showing 79 and 86% antioxidant effects in the DPPH and ferric thiocyanate assays, respectively. At the 1-wk time point, the 5 cheese preparations underwent sensory evaluation for odor, taste, texture, color, and overall quality, determined using a descriptive analysis by a trained panel (n=20). The addition of IBE resulted in some increases in extract odor and taste. Overall, IBE showed good potential as an antioxidant supplement for dairy products.
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•A robust one-step method is proposed to synthesize geopolymer-supported zeolites.•Zeolite yield was highly correlated with time, pressure, molarity and slag content.•Synthesized ...samples exhibited the characteristics of mesoporous materials.•A high adsorption capacity of 37.9 mg, Pb2+/g, bulk-type adsorbents was achieved.
The present study proposes a robust one-step hydrothermal treatment method for synthesis of high strength geopolymer-supported zeolites utilizing industrial by-products (fly ash and blast furnace slag), which can be potentially used as bulk-type solid adsorbents. The results revealed that the geopolymer-supported zeolites, possessing distinct strengths, zeolite phases (Na-P1, Na-chabazite, and analcime) and pore features depending on the mix design and synthesis conditions, can be easily synthesized employing the proposed one-step method. The geopolymer-supported zeolites exhibited the characteristics of mesoporous materials which are typically desired for commercial adsorbents. The maximum adsorption capacity for Pb2+ was found to be about 37.9 mg/g which is relatively higher than the other bulk-type adsorbents reported for Pb2+ to date. Since industrial by-products are used for synthesis of these materials, it will help in reducing the environmental hazards associated with the permanent disposal of such by-products, with an added advantage that these bulk-type solid adsorbents can be easily retrieved after use unlike granular adsorbents.
Mosquitoes in the Anopheles gambiae complex show rapid ecological and behavioral diversification, traits that promote malaria transmission and complicate vector control efforts. A high-density, ...genome-wide mosquito SNP-genotyping array allowed mapping of genomic differentiation between populations and species that exhibit varying levels of reproductive isolation. Regions near centromeres or within polymorphic inversions exhibited the greatest genetic divergence, but divergence was also observed elsewhere in the genomes. Signals of natural selection within populations were overrepresented among genomic regions that are differentiated between populations, implying that differentiation is often driven by population-specific selective events. Complex genomic differentiation among speciating vector mosquito populations implies that tools for genome-wide monitoring of population structure will prove useful for the advancement of malaria eradication.
We use extremely bright and ultrashort pulses from an x-ray free-electron laser (XFEL) to measure correlations in x rays scattered from individual bioparticles. This allows us to go beyond the ...traditional crystallography and single-particle imaging approaches for structure investigations. We employ angular correlations to recover the three-dimensional (3D) structure of nanoscale viruses from x-ray diffraction data measured at the Linac Coherent Light Source. Correlations provide us with a comprehensive structural fingerprint of a 3D virus, which we use both for model-based and ab initio structure recovery. The analyses reveal a clear indication that the structure of the viruses deviates from the expected perfect icosahedral symmetry. Our results anticipate exciting opportunities for XFEL studies of the structure and dynamics of nanoscale objects by means of angular correlations.
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