BINA

We integrate niobium nitride superconducting nanowire single-photon detectors (SNSPDs) on thin-film lithium niobate (LN) photonic waveguides. Further development of this technology may push towards more complex circuits and functionalities on this already promising platform.

The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the …

We present a theory of radiation in accelerated quantum electrodynamics which is manifestly thermalized at the accelerated temperature. Statistical analysis of a recent channeling radiation experiment implies the first observation of the Unruh effect.

We describe the growth of single crystals of the halide perovskites APbBr3, with varying ratios of Cs to methylammonium (MA) on the A site, by antisolvent vapor-assisted crystallization (AVC) and characterize the structural and compositional homogeneity of the grown crystals. We find improved thermostability for the Cs-rich mixed crystals and suggest that this is caused by a combination of locking-in of the relatively large MA in the smaller lattice of the Cs-rich material as well as by stronger hydrogen bonding between the nitrogen of MA and Br due to reduced lattice size and/or octahedral tilting with increased Cs. We also show that it is possible to grow either compositionally homogeneous crystals or core–shell, compositionally graded crystals by changing the ratio of antisolvent to solvent in the AVC method.

We report on a fundamental role of a non-normalized formal steady state, ie, an infinite invariant density, in a semi-Markov process where the state is determined by the interevent time of successive renewals. The state describes certain observables found in models of anomalous diffusion, eg, the velocity in the generalized Lévy walk model and the energy of a particle in the trap model. In our model, the interevent-time distribution follows a fat-tailed distribution, which makes the state value more likely to be zero because long interevent times imply small state values. We find two scaling laws describing the density for the state value, which accumulates in the vicinity of zero in the long-time limit. These laws provide universal behaviors in the accumulation process and give the exact expression of the infinite invariant density. Moreover, we provide two distributional limit theorems for time-averaged observables in these …

We demonstrate a new approach to carrier-envelope-offset detection in dispersion-engineered waveguides based on saturated second harmonic generation of femtosecond pulses. This technique simultaneously broadens both harmonics, resulting in coherent carrier-envelope-offset beatnotes across ~ 400-nm of bandwidth.

Hydrogen sensing in real environments is an important issue on the pathway toward the hydrogen economy. The use of semiconductor-based sensing layers has significantly advanced the detection limit of the H2 sensor, in part thanks to the additional use of catalytic metals which effectively dope their electron depletion layer. Nevertheless, these high-end sensors are highly sensitive to the environmental parameters (temperature and humidity) and require a complex fabrication process. Herein, we report a colloidal approach to the fabrication of indium-tin oxide combined with palladium-nickel or platinum nanoparticles sensing layer. The cross-sections of the sensing layers show the network of nanoparticles and voids responsible for the excellent sensing properties they display. The sensors show sensitivity from 4 % down to 70 ppm of H2 and repeatability in that range. Moreover, the sensors have a unique ability …

The search for therapeutic strategies to promote neuronal regeneration following injuries toward functional recovery is of great importance. Brief low-frequency electrical stimulation (ES) has been reported as a useful method to improve neuronal regeneration in different animal models; however, the effect of ES on single neuron behavior has not been shown. Here, we study the effect of brief ES on neuronal regeneration of the CNS of adult medicinal leeches. Studying the regeneration of selected sets of identified neurons allow us to quantify the ES effect per cell type at the single-cell level. Chains of the CNS that were subjected to cut injury were observed for 3 d, and the spontaneous regeneration was compared with the electrically stimulated injured chains. We show that the ES improves the efficiency of regeneration of Retzius cells, as larger masses of the total branching tree traverse the injury site with better …

Atox1 is a human copper metallochaperone that is responsible for transferring copper ions from the main human copper transporter, hCtr1, to ATP7A/B in the Golgi apparatus. Atox1 interacts with the Ctr1 C-terminal domain as a dimer, although it transfers the copper ions to ATP7A/B in a monomeric form. The copper binding site in the Atox1 dimer involves Cys12 and Cys15, while Lys60 was also suggested to play a role in the copper binding. We recently showed that Atox1 can adopt various conformational states, depending on the interacting protein. In the current study, we apply EPR experiments together with hybrid quantum mechanics–molecular mechanics molecular dynamics simulations using a recently developed semiempirical density functional theory approach, to better understand the effect of Atox1’s conformational states on copper coordination. We propose that the flexibility of Atox1 occurs owing to …

The compression of extended, coded sequences allows for laser ranging measurements with low peak power levels. Previous realizations of this approach were restricted by additive noise of direct, incoherent detection. In this work we bring together pulse sequence coding and optical coherent detection to achieve very high sensitivity. Collected sequences with an overall energy equivalent to only 800 photons are successfully compressed. The observed sensitivity agrees with analytic predictions. Compared with incoherent detection, measurement durations are reduced by four orders of magnitude. The protocol is suitable for laser ranging over tens of kilometers, depending on atmospheric conditions.

We demonstrate carrier-envelope offset frequency (/Ceo) stabilization of a modelocked laser using an integrated, dispersion engineered lithium niobate f-2f interferometer via simultaneous supercontinuum and second-harmonic generation with only 107 pJ pulse energy.

BackgroundThe etiology of major neurodevelopmental disorders (NMD) such as Schizophrenia and Autism is unclear with evidence supporting a combination of polygenic susceptibility and exposure to environmental risk which can impair neurodevelopment. Maternal immune activation (MIA) models in rodents are based on observations that viral infection during pregnancy causes an immune activation which puts the offspring at higher risk for developing SCZ. Here we investigate the transcriptional changes in a MIA model, to identify alteration during brain development that may precipitate disease onset.MethodsOn gestational day 9, pregnant C57BL6/J dams were injected with poly-I: C (5 mg/kg/ml) or saline (PolyI: C= 8, Control= 11). One cohort was allocated to behavioral testing of offspring in adulthood. The other cohort of dams was sacrificed 24-h after MIA. RNA was extracted and sequenced from the fetuses …

Terpene and terpenoid syntheses are challenging tasks because of the required multiple synthetic steps, exact functionalization, and difficult purification that reduce the yields. One of the propitious methods to tackle this problem is the synthesis of terpenes inside nanocapsules. Nanocapsules based on resorcinarene moieties have recently been employed experimentally to generate sesquiterpenes, but the improvement of product distribution control in such nanoreactors is currently challenging due to a lack of specificity. In the current work, we study the in-capsule reactions employing multiscale modeling techniques along with a high-temperature Langevin molecular dynamics simulation protocol as well as the potential of mean force using the umbrella sampling technique. Additionally, we generate a sesquiterpene database with information derived from quantum chemical calculations. Using these methods, we …

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.) 2017-06-28

Fluorescence detection, either involving propagating or near-field emission, is widely being used in spectroscopy, sensing, and microscopy. Total internal reflection fluorescence (TIRF) confines fluorescence excitation by an evanescent (near) field, and it is a popular contrast generator for surface-selective fluorescence assays. Its emission equivalent, supercritical angle fluorescence (SAF), is comparably less established, although it achieves a similar optical sectioning as TIRF does. SAF emerges when a fluorescing molecule is located very close to an interface and its near-field emission couples to the higher refractive index medium (n2 > n1) and becomes propagative. Then, most fluorescence is detectable on the side of the higher-index substrate, and a large fraction of this fluorescence is emitted into angles forbidden by Snell’s law. SAF, as well as the undercritical angle fluorescence (UAF; far-field emission …

The conserved signal recognition particle (SRP) cotranslationally delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum (ER). The molecular mechanism by which eukaryotic SRP transitions from cargo recognition in the cytosol to protein translocation at the ER is not understood. Here, structural, biochemical, and single-molecule studies show that this transition requires multiple sequential conformational rearrangements in the targeting complex initiated by guanosine triphosphatase (GTPase)–driven compaction of the SRP receptor (SR). Disruption of these rearrangements, particularly in mutant SRP54G226E linked to severe congenital neutropenia, uncouples the SRP/SR GTPase cycle from protein translocation. Structures of targeting intermediates reveal the molecular basis of early SRP-SR recognition and emphasize the role of eukaryote-specific elements in regulating targeting. Our results provide a molecular model for the structural and functional transitions of SRP throughout the targeting cycle and show that these transitions provide important points for biological regulation that can be perturbed in genetic diseases.

Splicing and alternative splicing of pre-mRNA are key sources in the formation of diversity in the human proteome. These processes have a central role in the regulation of the gene expression pathway. Yet, how spliceosomes are assembled on a multi-intronic pre-mRNA is at present not well understood. To study the spliceosomes assembled in vivo on transcripts with variable number of introns, we examined a series of three related transcripts derived from the β-globin gene, where two transcript types contained increasing number of introns, while one had only an exon. Each transcript had multiple MS2 sequence repeats that can be bound by the MS2 coat protein. Using our protocol for isolation of endogenous spliceosomes under native conditions from cell nuclei, we show that all three transcripts are found in supraspliceosomes – 21 MDa dynamic complexes, sedimenting at 200S in glycerol gradients, and composed of four native spliceosomes connected by the transcript. Affinity purification of complexes assembled on the transcript with most introns (termed E6), using the MS2-tag, confirmed the assembly of E6 in supraspliceosomes with components such as Sm proteins and PSF. Furthermore, splicing inhibition by spliceostatin A did not inhibit the assembly of supraspliceosomes on the E6 transcript, yet, increased the percentage of E6 pre-mRNA supraspliceosomes. These findings were corroborated in intact cells, using RNA FISH to detect the MS2-tagged E6 mRNA, together with GFP-tagged splicing factors, showing the assembly of splicing factors SRSF2, U1-70K and PRP8 onto the E6 transcripts under normal conditions and also when …

Page 3075. In the title, there was confusion, and we accidently used the wrong term “Oxidation” when we should have used “Oxygen”, as we did in the paper. Therefore, the title should be “Leveraging Commercial Silver Inks as Oxygen Reduction Reaction Catalysts in Alkaline Medium”.

This chapter reviews the research on antibacterial functionalization of textiles with inorganic nanoparticles by the sonochemical method. Sonochemical reactions are dependent on acoustic cavitation: the formation, growth, and explosive collapse of bubbles in irradiated liquids. Nanotechnology allows textiles to become multifunctional and produce fabrics with special functions—fabrics that provide ultraviolet protection and are antibacterial, easy to clean, water and stain repellent, and antiodor. Special efforts were made to search for green stabilizing agents in order to make the incorporation of silver into textiles an environmentally friendly process. The bubbles created during sonochemical irradiation of the liquid collapse near the surface of the solid substrate. Raman spectroscopy was also used to characterize silver-nylon nanocomposites. Natural wool fibers under proper temperature and humidity are a very good …

We use Langevin dynamics simulations to study dense 2d systems of particles with both size and energy polydispersity. We compare two types of bidisperse systems which differ in the correlation between particle size and interaction parameters: in one system big particles have high interaction parameters and small particles have low interaction parameters, while in the other system the situation is reversed. We study the different phases of the two systems and compare them to those of a system with size but not energy bidispersity. We show that, depending on the strength of interaction between big and small particles, cooling to low temperatures yields either homogeneous glasses or mosaic crystals. We find that systems with low mixing interaction, undergo partial freezing of one of the components at intermediate temperatures, and that while this phenomenon is energy-driven in both size and energy bidisperse systems, it is controlled by entropic effects in systems with size bidispersity only. View Full-Text