Vertical arrays of direct band gap III-V semiconductor nanowires (NWs) hold the prospect of cheap and efficient next-generation photovoltaics, and guidelines for successful light-management are ...needed. Here, we use InP NWs as a model system and find, through electrodynamic modeling, general design principles for efficient absorption of sun light in nanowire arrays by systematically varying the nanowire diameter, the nanowire length, and the array period. Most importantly, we discover the existence of specific band-gap dependent diameters, 170 nm and 410 nm for InP, for which the absorption of sun light in the array is optimal, irrespective of the nanowire length. At these diameters, the individual InP NWs of the array absorb light strongly for photon energies just above the band gap energy due to a diameter-tunable nanophotonic resonance, which shows up also for other semiconductor materials of the NWs. Furthermore, we find that for maximized absorption of sun light, the optimal period of the array increases with nanowire length, since this decreases the insertion reflection losses.
Background and purpose
The aim was to describe the clinical, radiological and pathological features of an autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.
Methods
Data from 19 ...patients with positive GFAP‐immunoglobulin G in cerebrospinal fluid (CSF) were retrospectively analyzed.
Results
The main disease manifestations included myelitis (68.4%), headache (63.2%), abnormal vision (63.2%), fever (52.6%), ataxia (36.8%), psychosis (31.6%), dyskinesia (15.8%), dementia (15.8%) and seizure (10.5%). Seventeen patients had brain abnormalities (89.5%), of which eight (42.1%) revealed the characteristic radial enhancing and laminar patterns. Cortical abnormalities were found in four patients (21.1%). Other abnormalities were found in the hypothalamus, midbrain, pons, medulla cerebellum, meninges and skull. Eleven patients had longitudinally extensive spinal cord lesions. CSF abnormalities were detected in all patients. Pathological examinations of four patients revealed extensive inflammation, with prominent perivascular B cells and T cells. Abundant antibody‐secreting cells were noted in the interstitial and perivascular spaces. Immunohistochemical analysis showed loss of astrocytes and neurons.
Conclusion
The present patients with positive GFAP‐immunoglobulin G are highly similar to autoimmune GFAP astrocytopathy, described in a recent report. The features of the neuropathology and immunopathology of GFAP astrocytopathies were perivascular inflammation and loss of astrocytes and neurons.
Click here to view the accompanying paper in this volume.
The objectives of this study were to synthesize new quaternary ammonium methacrylates (QAMs) with systematically varied alkyl chain lengths (CL) and to investigate, for the first time, the CL effects ...on antibacterial efficacy, cytotoxicity, and dentin bond strength of bonding agents. QAMs were synthesized with CL of 3 to 18 and incorporated into Scotchbond Multi-Purpose (SBMP) bonding agent. The cured resins were inoculated with Streptococcus mutans. Bacterial early attachment was investigated at 4 hrs. Biofilm colony-forming units (CFU) were measured after 2 days. With CL increasing from 3 to 16, the minimum inhibitory concentration and minimum bactericidal concentration were decreased by 5 orders of magnitude. Incorporating QAMs into SBMP reduced bacterial early attachment, with the least colonization at CL = 16. Biofilm CFU for CL = 16 was 4 log lower than SBMP control (p < .05). All groups had similar dentin bond strengths (p > .1). The new antibacterial materials had fibroblast/odontoblast viability similar to that of commercial controls. In conclusion, increasing the chain length of new QAMs in bonding agents greatly increased the antibacterial efficacy. A reduction in Streptococcus mutans biofilm CFU by 4 log could be achieved, without compromising bond strength and cytotoxicity. New QAM-containing bonding agents are promising for a wide range of restorations to inhibit biofilms.
Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 ...activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the human CB2-Gi signaling complex bound to the agonist WIN 55,212-2. The 3D structure reveals the binding mode of WIN 55,212-2 and structural determinants for distinguishing CB2 agonists from antagonists, which are supported by a pair of rationally designed agonist and antagonist. Further structural analyses with computational docking results uncover the differences between CB2 and CB1 in receptor activation, ligand recognition, and Gi coupling. These findings are expected to facilitate rational structure-based discovery of drugs targeting the cannabinoid system.
Display omitted
•3.2-Å cryo-EM structure of the CB2-Gi complex bound to potent agonist WIN 55,212-2•Algorithm developed for quantitative characterization of binding residues•Structural determinants for distinguishing CB2 agonists from antagonists•CB2-Gi binding features and different activation mechanisms of CB2 and CB1
The 3D structure of the agonist-bound CB2-Gi signaling complex provides insight into the key residues involved in ligand recognition and the distinction of agonists and antagonists critical for facilitating rational design of drugs targeting the cannabinoid system.
Nanoscale near-infrared photodetectors are attractive for their potential applications in integrated optoelectronic devices. Here we report the synthesis of GaSb/GaInSb p–n heterojunction ...semiconductor nanowires for the first time through a controllable chemical vapor deposition (CVD) route. Based on these nanowires, room-temperature, high-performance, near-infrared photodetectors were constructed. The fabricated devices show excellent light response in the infrared optical communication region (1.55 μm), with an external quantum efficiency of 104, a responsivity of 103 A/W, and a short response time of 2 ms, which shows promising potential applications in integrated photonics and optoelectronics devices or systems.
The long non-coding RNA, HOTTIP, has an important role in tumorigenesis. It is known that HOTTIP regulates HOX gene family; however, its regulatory mechanism in esophageal squamous cell carcinoma ...(ESCC) remains elusive. In this study, we investigated the role of HOTTIP in ESCC and observed that HOTTIP/HOXA13 was upregulated in ESCC and promoted cell proliferation and metastasis in vivo and in vitro. Interestingly, harboring a miR-30b-binding site, HOTTIP as a molecular sponge mainly regulated miR-30b level in the nucleus and modulated the repression of HOXA13 mediated by miR-30b in the cytoplasm, resulting in the positive HOTTIP/HOXA13 correlation. In addition, HOTTIP upregulated snail1 by competitively binding miR-30b, subsequently promoting epithelial-mesenchymal transition (EMT) and invasion. HOTTIP directly bound the adaptor protein WDR5 and drove histone H3 lysine 4 trimethylation and HOXA13 gene transcription in ESCC cells. In conclusion, our findings indicated that HOTTIP modulated HOXA13 at both the transcriptional and posttranscriptional levels in ESCC cells and HOTTIP-miR-30b-HOXA13 axis may serve as potential diagnostic markers or drug targets for ESCC therapies.
Leukotriene B4 receptor 1 (BLT1) plays crucial roles in the acute inflammatory responses and is a valuable target for anti-inflammation treatment, however, the mechanism by which leukotriene B4 ...(LTB4) activates receptor remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structure of the LTB4 -bound human BLT1 in complex with a G
protein in an active conformation at resolution of 2.91 Å. In combination of molecule dynamics (MD) simulation, docking and site-directed mutagenesis, our structure reveals that a hydrogen-bond network of water molecules and key polar residues is the key molecular determinant for LTB4 binding. We also find that the displacement of residues M101
and I271
to the center of receptor, which unlock the ion lock of the lower part of pocket, is the key mechanism of receptor activation. In addition, we reveal a binding site of phosphatidylinositol (PI) and discover that the widely open ligand binding pocket may contribute the lack of specificity and efficacy for current BLT1-targeting drug design. Taken together, our structural analysis provides a scaffold for understanding BLT1 activation and a rational basis for designing anti-leukotriene drugs.
The development of novel analgesics with improved safety profiles to combat the opioid epidemic represents a central question to G protein coupled receptor structural biology and pharmacology: What ...chemical features dictate G protein or β-arrestin signaling? Here we use adaptively biased molecular dynamics simulations to determine how fentanyl, a potent β-arrestin biased agonist, binds the μ-opioid receptor (μOR). The resulting fentanyl-bound pose provides rational insight into a wealth of historical structure-activity-relationship on its chemical scaffold. Following an in-silico derived hypothesis we found that fentanyl and the synthetic opioid peptide DAMGO require M153 to induce β-arrestin coupling, while M153 was dispensable for G protein coupling. We propose and validate an activation mechanism where the n-aniline ring of fentanyl mediates μOR β-arrestin through a novel M153 "microswitch" by synthesizing fentanyl-based derivatives that exhibit complete, clinically desirable, G protein biased coupling. Together, these results provide molecular insight into fentanyl mediated β-arrestin biased signaling and a rational framework for further optimization of fentanyl-based analgesics with improved safety profiles.
Nutrient overenrichment has led to dramatic increases in harmful cyanobacterial blooms, creating serious threats to drinking water supplies, ecological and economic sustainability of freshwater ...ecosystems. Nutrient-cyanobacterial bloom interactions were examined in eutrophic Lake Taihu, China. In situ microcosm nutrient dilution bioassays and mesocosm nutrient addition experiments were conducted to determine nitrogen (N) and phosphorus (P) concentration and load thresholds needed to control cyanobacterial bloom formation. Blooms were dominated by toxic, non N2 fixing Microcystis spp, from May to December. Dilution bioassays showed seasonality in nutrient limitation, with P-availability controlling prebloom spring conditions and N-availability controlling summer-fall blooms. Nutrient dilution and enrichment bioassays indicated that total nitrogen (TN) and total phosphorus (TP) concentration thresholds should be targeted at below 0.80 mg L–1 and 0.05 mg L–1, respectively, to limit intrinsic growth rates of Microcystis dominated blooms. Based on estimates of nutrient loading and observed stoichiometry of phytoplankton biomass, 61–71% TN and 20–46% TP reduction are necessary to bring Taihu’s phytoplankton biomass to “acceptable” sub-bloom conditions of less than 20 μg L–1 chlorophyll a.
PDF
