81-Element single-layer reflectarray with double-ring phasing elements for wideband applications

A microstrip reflectarray antenna utilizes a planar array of printed patch elements and a conventional prime or offset feed to form an alternative to the parabolic reflector [1]. It transforms the spherical wave of the feed into the planar wave by employing microstrip patch elements as radiators and phase shifters. Due to the use of planar technology, it offers a good balance between conventional reflector antennas and phased arrays. Because it uses many radiating elements it provides flexibility with respect to radiation pattern formation [2-4]. Its disadvantage is a limited operational bandwidth, which for the case of moderate gain is mainly due to a limited phase range and a high phase slope of the elements. In the wave transformation process, a full phasing range of 360° is desirable for unit cells containing patch elements. However, a variable size patch antenna developed on a single layer substrate offers a phasing range of about 300°. To overcome this problem, multilayer substrates including stacked variable-size patches for phasing the unit cells of a reflectarray have been devised to extend the phase range to multiples of 360°. The multi-layer approach with stacked patches not only extends the phase range but also reduces the slope of the phase curve as a function of patch dimensions [5-6]. However, the use of multi-layer substrates means that in practice layers of the reflectarray have to be manufactured separately and the assembly should leave no air gaps. This results in an elaborate and expensive manufacturing process. To overcome this problem, printed double-ring elements to form a single-layer reflectarray have been proposed. The double rings improve the phasing range of unit cells by utilizing multi-resonance behaviour. The extended range for unit cells containing double-ring elements has been demonstrated for the case of normal (TEM) wave incidence [7]. The assumption of normal incidence is less accurate for peripheral elements. Therefore in [8], TE and TM waves were considered to obtain an oblique incidence to obtain more accurate phasing characteristics of unit cells. © 2010 IEEE

Investigations into a circular ring with variable length arc element for phasing wideband reflectarray

A new phasing element for use in a wideband microstrip reflectarray is described. It is formed by a variable length arc attached to a fixed size circular ring. It is shown that the new phasing element offers a double resonance with an increased phasing range that is welcome in the reflectarray phase compensation procedure. The extended phase range enables the use of a thicker substrate to obtain a slower phase slope and thus an increased operational bandwidth of the reflectarrray. In the proposed approach, an increased reflectarray thickness is achieved using a foam layer placed underneath the substrate laminate carrying the phasing elements pattern. The usefulness of the newly proposed phasing element is demonstrated in the design of a 13x13 element reflectarray. Full wave EM simulations carried out with CST Microwave Studio confirm a wideband operation of the designed reflectarray

Transmembrane TM3b of Mechanosensitive Channel MscS Interacts With Cytoplasmic Domain Cyto-Helix

The mechanosensitive channel MscS functions as an osmolyte emergency release-valve in the event of a sudden decrease in external environmental osmolarity. MscS has served as a paradigm for studying how channel proteins detect and respond to mechanical stimuli. However, the inter-domain interactions and structural rearrangements that occur in the MscS gating process remain largely unknown. Here, we determined the interactions between the transmembrane domain and cytoplasmic domain of MscS. Using in vivo cellular viability, single-channel electrophysiological recording, and cysteine disulfide trapping, we demonstrated that N117 of the TM3b helix and N167 of the Cyto-helix are critical residues that function at the TM3b-Cyto helix interface. In vivo downshock assays showed that double cysteine substitution at N117 and N167 failed to rescue the osmotic-lysis phenotype of cells in acute osmotic downshock. Single-channel recordings demonstrated that cysteine cross-linking of N117C and N167C led to a non-conductive channel. Consistently, coordination of the histidines of N117H and N167H caused a decrease in channel gating. Moreover, cross-linked N117 and N167 altered the gating of the severe gain-of-function mutant L109S. Our results demonstrate that N117–N167 interactions stabilize the inactivation state by an association of TM3b segments with β-domains of the cytoplasmic region, providing further insights into the gating mechanism of the MscS channel

Clinical analysis and functional characterization of KCNQ2-related developmental and epileptic encephalopathy

BackgroundDevelopmental and epileptic encephalopathy (DEE) is a condition characterized by severe seizures and a range of developmental impairments. Pathogenic variants in KCNQ2, encoding for potassium channel subunit, cause KCNQ2-related DEE. This study aimed to examine the relationships between genotype and phenotype in KCNQ2-related DEE.MethodsIn total, 12 patients were enrolled in this study for genetic testing, clinical analysis, and developmental evaluation. Pathogenic variants of KCNQ2 were characterized through a whole-cell electrophysiological recording expressed in Chinese hamster ovary (CHO) cells. The expression levels of the KCNQ2 subunit and its localization at the plasma membrane were determined using Western blot analysis.ResultsSeizures were detected in all patients. All DEE patients showed evidence of developmental delay. In total, 11 de novo KCNQ2 variants were identified, including 10 missense variants from DEE patients and one truncating variant from a patient with self-limited neonatal epilepsy (SeLNE). All variants were found to be loss of function through analysis of M-currents using patch-clamp recordings. The functional impact of variants on M-current in heteromericKCNQ2/3 channels may be associated with the severity of developmental disorders in DEE. The variants with dominant-negative effects in heteromeric channels may be responsible for the profound developmental phenotype.ConclusionThe mechanism underlying KCNQ2-related DEE involves a reduction of the M-current through dominant-negative effects, and the severity of developmental disorders in DEE may be predicted by the impact of variants on the M-current of heteromericKCNQ2/3 channels

Endovascular Metal Devices for the Treatment of Cerebrovascular Diseases

Cerebrovascular disease involves various medical disorders that obstruct brain blood vessels or deteriorate cerebral circulation, resulting in ischemic or hemorrhagic stroke. Nowadays, platinum coils with or without biological modification have become routine embolization devices to reduce the risk of cerebral aneurysm bleeding. Additionally, many intracranial stents, flow diverters, and stent retrievers have been invented with uniquely designed structures. To accelerate the translation of these devices into clinical usage, an in‐depth understanding of the mechanical and material performance of these metal‐based devices is critical. However, considering the more distal location and tortuous anatomic characteristics of cerebral arteries, present devices still risk failing to arrive at target lesions. Consequently, more flexible endovascular devices and novel designs are under urgent demand to overcome the deficiencies of existing devices. Herein, the pros and cons of the current structural designs are discussed when these devices are applied to the treatment of diseases ranging broadly from hemorrhages to ischemic strokes, in order to encourage further development of such kind of devices and investigation of their use in the clinic. Moreover, novel biodegradable materials and drug elution techniques, and the design, safety, and efficacy of personalized devices for further clinical applications in cerebral vasculature are discussed.Peer reviewe

Laser-Activatable CuS Nanodots to Treat Multidrug-Resistant Bacteria and Release Copper Ion to Accelerate Healing of Infected Chronic Nonhealing Wounds

Chronic nonhealing wounds have imposed serious challenges in the clinical practice, especially for the patients infected with multidrug-resistant microbes. Herein, we developed an ultrasmall copper sulfide (covellite) nanodots (CuS NDs) based dual functional nanosystem to cure multidrug-resistant bacteria-infected chronic nonhealing wound. The nanosystem could eradicate multidrug-resistant bacteria and expedite wound healing simultaneously owing to the photothermal effect and remote control of copper-ion release. The antibacterial results indicated that the combination treatment of photothermal CuS NDs with photothermal effect initiated a strong antibacterial effect for drug-resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase Escherichia coli both in vitro and in vivo. Meanwhile, the released Cu2+ could promote fibroblast cell migration and endothelial cell angiogenesis, thus accelerating wound-healing effects. In MRSA-infected diabetic mice model, the nanosystem exhibited synergistic wound healing effect of infectious wounds in vivo and demonstrated negligible toxicity and nonspecific damage to major organs. The combination of ultrasmall CuS NDs with photothermal therapy displayed enhanced therapeutic efficacy for chronic nonhealing wound in multidrug-resistant bacterial infections, which may represent a promising class of antibacterial strategy for clinical translation.Peer reviewe

Multistage signal-interactive nanoparticles improve tumor targeting through efficient nanoparticle-cell communications

Communication between biological components is critical for homeostasis maintenance among the convergence of complicated bio-signals. For therapeutic nanoparticles (NPs), the general lack of effective communication mechanisms with the external cellular environment causes loss of homeostasis, resulting in deprived autonomy, severe macrophage-mediated clearance, and limited tumor accumulation. Here, we develop a multistage signal-interactive system on porous silicon particles through integrating the Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide into a hierarchical chimeric signaling interface with “don’t eat me” and “eat me” signals. This biochemical transceiver can act as both the signal receiver for amantadine to achieve NP transformation and signal conversion as well as the signal source to present different signals sequentially by reversible self-mimicking. Compared with the non-interactive controls, these signal-interactive NPs loaded with AS1411 and tanespimycin (17-AAG) as anticancer drugs improve tumor targeting 2.8-fold and tumor suppression 6.5-fold and showed only 51% accumulation in the liver with restricted hepatic injury.Peer reviewe

Multistage signal-interactive nanoparticles improve tumor targeting through efficient nanoparticle-cell communications

Communication between biological components is critical for homeostasis maintenance among the convergence of complicated bio-signals. For therapeutic nanoparticles (NPs), the general lack of effective communication mechanisms with the external cellular environment causes loss of homeostasis, resulting in deprived autonomy, severe macrophage-mediated clearance, and limited tumor accumulation. Here, we develop a multistage signal-interactive system on porous silicon particles through integrating the Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide into a hierarchical chimeric signaling interface with “don’t eat me” and “eat me” signals. This biochemical transceiver can act as both the signal receiver for amantadine to achieve NP transformation and signal conversion as well as the signal source to present different signals sequentially by reversible self-mimicking. Compared with the non-interactive controls, these signal-interactive NPs loaded with AS1411 and tanespimycin (17-AAG) as anticancer drugs improve tumor targeting 2.8-fold and tumor suppression 6.5-fold and showed only 51% accumulation in the liver with restricted hepatic injury.</p

Mifepristone Increases the Cytotoxicity of Uterine Natural Killer Cells by Acting as a Glucocorticoid Antagonist via ERK Activation

Background: Mifepristone (RU486), a potent antagonist of progesterone and glucocorticoids, is involved in immune regulation. Our previous studies demonstrated that mifepristone directly augments the cytotoxicity of human uterine natural killer (uNK) cells. However, the mechanism responsible for this increase in cytotoxicity is not known. Here, we explored whether the increased cytotoxicity in uNK cells produced by mifepristone is due to either anti-progesterone or anti-glucocorticoid activity, and also investigated relevant changes in the mitogen-activated protein kinase (MAPK) pathway. Methodology/Principal Findings: Uterine NK cells were isolated from decidual samples and incubated with different concentrations of progesterone, cortisol, or mifepristone. The cytotoxicity and perforin expression of uNK cells were detected by mitochondrial lactate dehydrogenase-based MTS staining and flow cytometry assays, respectively. Phosphorylation of components of the MAPK signaling pathway was detected by Western blot. Cortisol attenuated uNK cell-mediated cytotoxicity in a concentration-dependent manner whereas progesterone had no effect. Mifepristone alone increased the cytotoxicity and perforin expression of uNK cells; these effects were blocked by cortisol. Furthermore, mifepristone increased the phosphorylation of ERK1/2 in a cortisol-reversible manner. Specific ERK1/2 inhibitor PD98059 or U0126 blocked cortisol- and mifepristone-induced responses in uNK cells

Astroglial-Kir4.1 in Lateral Habenula Drives Neuronal Bursts to Mediate Depression

International audienceEnhanced bursting activity of neurons in the lateral habenula (LHb) is essential in driving depression-like behaviours, but the cause of this increase has been unknown. Here, using a high-throughput quantitative proteomic screen, we show that an astroglial potassium channel (Kir4.1) is upregulated in the LHb in rat models of depression. Kir4.1 in the LHb shows a distinct pattern of expression on astrocytic membrane processes that wrap tightly around the neuronal soma. Electrophysiology and modelling data show that the level of Kir4.1 on astrocytes tightly regulates the degree of membrane hyperpolarization and the amount of bursting activity of LHb neurons. Astrocyte-specific gain and loss of Kir4.1 in the LHb bidirectionally regulates neuronal bursting and depression-like symptoms. Together, these results show that a glia–neuron interaction at the perisomatic space of LHb is involved in setting the neuronal firing mode in models of a major psychiatric disease. Kir4.1 in the LHb might have potential as a target for treating clinical depression