Enhanced thermoelectric figure of merit in vertical graphene junctions

In this work, we investigate thermoelectric properties of junctions consisting of two partially overlapped graphene sheets coupled to each other in the cross-plane direction. It is shown that because of the weak van-der Waals interactions between graphene layers, the phonon conductance in these junctions is strongly reduced, compared to that of single graphene layer structures, while their electrical performance is weakly affected. By exploiting this effect, we demonstrate that the thermoelectric figure of merit can reach values higher than 1 at room temperature in junctions made of gapped graphene materials, for instance, graphene nanoribbons and graphene nanomeshes. The dependence of thermoelectric properties on the junction length is also discussed. This theoretical study hence suggests an efficient way to enhance thermoelectric efficiency of graphene devices.Comment: 6 pages, 4 figures, submitte

Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates.

Retinal gene therapy using adeno-associated viruses (AAVs) is constrained by the mode of viral vector delivery. Intravitreal AAV injections are impeded by the internal limiting membrane barrier, while subretinal injections require invasive surgery and produce a limited region of therapeutic effect. In this study, we introduce a novel mode of ocular gene delivery in rhesus macaques using transscleral microneedles to inject AAV8 into the subretinal or suprachoroidal space, a potential space between the choroid and scleral wall of the eye. Using in vivo imaging, we found that suprachoroidal AAV8 produces diffuse, peripheral expression in retinal pigment epithelial (RPE) cells, but it elicited local infiltration of inflammatory cells. Transscleral subretinal injection of AAV8 using microneedles leads to focal gene expression with transduction of RPE and photoreceptors, and minimal intraocular inflammation. In comparison, intravitreal AAV8 shows minimal transduction of retinal cells, but elicits greater systemic humoral immune responses. Our study introduces a novel mode of transscleral viral delivery that can be performed without vitreoretinal surgery, with focal or diffuse transgene expression patterns suitable for different applications. The decoupling of local and systemic immune responses reveals important insights into the immunological consequences of AAV delivery to different ocular compartments surrounding the blood-retinal barrier

Structural and Functional Analysis of a β2-Adrenergic Receptor Complex with GRK5.

The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor (β2AR). These studies revealed a dynamic mechanism of complex formation that involves large conformational changes in the GRK5 RH/catalytic domain interface upon receptor binding. These changes facilitate contacts between intracellular loops 2 and 3 and the C terminus of the β2AR with the GRK5 RH bundle subdomain, membrane-binding surface, and kinase catalytic cleft, respectively. These studies significantly contribute to our understanding of the mechanism by which GRKs regulate the function of activated GPCRs. PAPERCLIP

Deterministic Raman crosstalk effects in amplified wavelength division multiplexing transmission

We study the deterministic effects of Raman-induced crosstalk in amplified wavelength division multiplexing (WDM) optical fiber transmission lines. We show that the dynamics of pulse amplitudes in an N-channel transmission system is described by an N-dimensional predator-prey model. We find the equilibrium states with non-zero amplitudes and prove their stability by obtaining the Lyapunov function. The stability is independent of the exact details of the approximation for the Raman gain curve. Furthermore, we investigate the impact of cross phase modulation and Raman self and cross frequency shifts on the dynamics and establish the stability of the equilibrium state with respect to these perturbations. Our results provide a quantitative explanation for the robustness of differential-phase-shift-keyed WDM transmission against Raman crosstalk effects.Comment: 34 pages and 12 figures. Revised paper. Submitted to Optics Communication

A pair of peptides inhibits seeding of the hormone transporter transthyretin into amyloid fibrils

The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloid-driving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach.This work was supported by Amyloidosis Foundation Grant 20160759 and 20170827, National Institutes of Health Grant R01-AG048120, and The Howard Hughes Medical Institute. The authors and UCLA have filed an international patent application for the TTR inhibitors (number PCT/US17/40103). D. S. E. is an advisor and equity holder of ADRx, Inc. L. S. is a consultant of ADRx, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.info:eu-repo/semantics/publishedVersio

Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

OBJECTIVES: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. METHODS: Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. RESULTS: Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. CONCLUSIONS: We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission

Spin transfer torque generated magnetic droplet solitons (invited)

We present recent experimental and numerical advancements in the understanding of spin transfer torque generated magnetic droplet solitons. The experimental work focuses on nano-contact spin torque oscillators (NC-STOs) based on orthogonal (pseudo) spin valves where the Co fixed layer has an easy-plane anisotropy, and the [Co/Ni] free layer has a strong perpendicular magnetic anisotropy. The NC-STO resistance and microwave signal generation are measured simultaneously as a function of drive current and applied perpendicular magnetic field. Both exhibit dramatic transitions at a certain current dependent critical field value, where the microwave frequency drops 10 GHz, modulation sidebands appear, and the resistance exhibits a jump, while the magnetoresistance changes sign. We interpret these observations as the nucleation of a magnetic droplet soliton with a large fraction of its magnetization processing with an angle greater than 90°, i.e., around a direction opposite that of the applied field. This interpretation is corroborated by numerical simulations. When the field is further increased, we find that the droplet eventually collapses under the pressure from the Zeeman energy

Prototyping of DSSDs for Particle Tracking and Spectroscopy within the EXL Project at Fair

Prototype double-sided silicon strip detectors (DSSD$s$) of 300 $\mu$m thickness produced at PTI St. Petersburg (Russia) were tested for the use as position sensitive, $\Delta E$ and E detectors for tracking and particle identification in the EXL (EXotic nuclei studied in Light-ion induced reactions at the NESR storage ring) setup at the FAIR (Facility for Antiproton and Ion Research) project at GSI. We describe the characteristics of detectors with $16 \times 16,\;64\times 64$ and $64\times 16$ strips, respectively. The response of these detectors for $^{241}$Am $\alpha$ particles injected either from the p or n side was examined. The test measurements were performed partially at GSI and the University of Edinburgh. A first in-beam test with a proton beam of 50 MeV with the latter two DSSDs and two 6.5 mm thick Si(Li) detectors was also done at KVI Groningen, the Netherlands. The results reveal good spectroscopic properties of these detectors