A space division multiplexed free-space-optical communication system that can auto-locate and fully self align with a remote transceiver

Free-Space Optical (FSO) systems offer the ability to distribute high speed digital links into remote and rural communities where terrain, installation cost or infrastructure security pose critical hurdles to deployment. A challenge in any point-to-point FSO system is initiating and maintaining optical alignment from the sender to the receiver. In this paper we propose and demonstrate a low-complexity self-aligning FSO prototype that can completely self-align with no requirement for initial manual positioning and could therefore form the opto-mechanical basis for a mesh network of optical transceivers. The prototype utilises off-the-shelf consumer electrical components and a bespoke alignment algorithm. We demonstrate an eight fibre spatially multiplexed link with a loss of 15 dB over 210 m

Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer's patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability

The author's final peer reviewed version can be found by following the URI link. The Publisher's final version can be found by following the DOI link.Aims Amyloid β oligomers (AβO) are potent modulators of Alzheimer’s pathology, yet their impact on one of the earliest brain regions to exhibit signs of the condition, the locus coeruleus (LC), remains to be determined. Of particular importance is whether AβO impact the spontaneous excitability of LC neurons. This parameter determines brain‐wide noradrenaline (NA) release, and thus NA‐mediated brain functions, including cognition, emotion and immune function, which are all compromised in Alzheimer’s. Therefore, the aim of the study was to determine the expression profile of AβO in the LC of Alzheimer’s patients and to probe their potential impact on the molecular and functional correlates of LC excitability, using a mouse model of increased Aβ production (APP‐PSEN1). Methods and Results Immunohistochemistry and confocal microscopy, using AβO‐specific antibodies, confirmed LC AβO expression both intraneuronally and extracellularly in both Alzheimer’s and APP‐PSEN1 samples. Patch clamp electrophysiology recordings revealed that APP‐PSEN1 LC neuronal hyperexcitability accompanied this AβO expression profile, arising from a diminished inhibitory effect of GABA, due to impaired expression and function of the GABA‐A receptor (GABAAR) α3 subunit. This altered LC α3‐GABAAR expression profile overlapped with AβO expression in samples from both APP‐PSEN1 mice and Alzheimer’s patients. Finally, strychnine‐sensitive glycine receptors (GlyRs) remained resilient to Aβ‐induced changes and their activation reversed LC hyperexcitability. Conclusions The data suggest a close association between AβO and α3‐GABAARs in the LC of Alzheimer’s patients, and their potential to dysregulate LC activity, thereby contributing to the spectrum of pathology of the LC‐NA system in this condition

Consequences of a telomerase-related fitness defect and chromosome substitution technology in yeast synIX strains

We describe the complete synthesis, assembly, debugging, and characterization of a synthetic 404,963 bp chromosome, synIX (synthetic chromosome IX). Combined chromosome construction methods were used to synthesize and integrate its left arm (synIXL) into a strain containing previously described synIXR. We identified and resolved a bug affecting expression of EST3, a crucial gene for telomerase function, producing a synIX strain with near wild-type fitness. To facilitate future synthetic chromosome consolidation and increase flexibility of chromosome transfer between distinct strains, we combined chromoduction, a method to transfer a whole chromosome between two strains, with conditional centromere destabilization to substitute a chromosome of interest for its native counterpart. Both steps of this chromosome substitution method were efficient. We observed that wild-type II tended to co-transfer with synIX and was co-destabilized with wild-type IX, suggesting a potential gene dosage compensation relationship between these chromosomes. </p

Advantages of Randomization in Coherent Quantum Dynamical Control

Control scenarios have been identified where the use of randomized design may substantially improve the performance of dynamical decoupling methods [L. F. Santos and L. Viola, Phys. Rev. Lett. {\bf 97}, 150501 (2006)]. Here, by focusing on the suppression of internal unwanted interactions in closed quantum systems, we review and further elaborate on the advantages of randomization at long evolution times. By way of illustration, special emphasis is devoted to isolated Heisenberg-coupled chains of spin-1/2 particles. In particular, for nearest-neighbor interactions, two types of decoupling cycles are contrasted: inefficient averaging, whereby the number of control actions increases exponentially with the system size, and efficient averaging associated to a fixed-size control group. The latter allows for analytical and numerical studies of efficient decoupling schemes created by exploiting and merging together randomization and deterministic strategies, such as symmetrization, concatenation, and cyclic permutations. Notably, sequences capable to remove interactions up to third order are explicitly constructed. The consequences of faulty controls are also analyzed.Comment: 27 pages, 7 figure

Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions

The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.0 chromosomes assembled. Here, we describe the consolidation of multiple synthetic chromosomes using advanced endoreduplication intercrossing with tRNA expression cassettes to generate a strain with 6.5 synthetic chromosomes. The 3D chromosome organization and transcript isoform profiles were evaluated using Hi-C and long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or ‘‘CRISPR D-BUGS,’’ to map phenotypic variants caused by specific designer modifications, known as ‘‘bugs.’’ We first fine-mapped a bug in synthetic chromosome II (synII) and then discovered a combinatorial interaction associated with synIII and synX, revealing an unexpected genetic interaction that links transcriptional regulation, inositol metabolism, and tRNASer CGA abundance. Finally, to expedite consolidation, we employed chromosome substitution to incorporate the largest chromosome (synIV), thereby consolidating &gt;50% of the Sc2.0 genome in one strain </p

Manipulating the 3D organization of the largest synthetic yeast chromosome

Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field. Here, we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast chromosome resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction. Besides the drastic sequence changes, we further manipulated the 3D structure of synIV to explore spatial gene regulation. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of synIV sheds light on higher-order architectural design of the synthetic genomes. </p

Cold Induces Micro- and Nano-Scale Reorganization of Lipid Raft Markers at Mounds of T-Cell Membrane Fluctuations

Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly characterized. Using the NSOM/QD and confocal imaging systems, we found that cold caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59 for protein, from the peripheral part of microdomains to the central part on Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3- to 2/3-fold) of the nanoclusters of lipid raft markers and even the colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced lateral rearrangement/coalescence of raft-related membrane heterogeneity. The cold-induced re-distribution of lipid raft markers under a nearly-natural condition provide clues for their alternations, and help to propose a model in which raft lipids associate themselves or interact with protein components to generate functional membrane heterogeneity in response to stimulus. The data also underscore the possible cold-induced artifacts in early-described cold-related experiments and the detergent-resistance-based analyses of lipid rafts at 4°C, and provide a biophysical explanation for recently-reported cold-induced activation of signaling pathways in T cells. Importantly, our fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers distributed and re-distributed at mounds but not depressions of T-cell membrane fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts provides spatial advantage for lipid rafts or contact molecules interacting readily with neighboring cells or free molecules

Optimized Dynamical Decoupling in a Model Quantum Memory

We present experimental measurements on a model quantum system that demonstrate our ability to dramatically suppress qubit error rates by the application of optimized dynamical decoupling pulse sequences in a variety of experimentally relevant noise environments. We provide the first demonstration of an analytically derived pulse sequence developed by Uhrig, and find novel sequences through active, real-time experimental feedback. These new sequences are specially tailored to maximize error suppression without the need for a priori knowledge of the ambient noise environment. We compare these sequences against the Uhrig sequence, and the well established CPMG-style spin echo, demonstrating that our locally optimized pulse sequences outperform all others under test. Numerical simulations show that our locally optimized pulse sequences are capable of suppressing errors by orders of magnitude over other existing sequences. Our work includes the extension of a treatment to predict qubit decoherence under realistic conditions, including the use of finite-duration, square $\pi$ pulses, yielding strong agreement between experimental data and theory for arbitrary pulse sequences. These results demonstrate the robustness of qubit memory error suppression through dynamical decoupling techniques across a variety of qubit technologies.Comment: Subject to press embarg

FAIR Data Pipeline: provenance-driven data management for traceable scientific workflows

Modern epidemiological analyses to understand and combat the spread of disease depend critically on access to, and use of, data. Rapidly evolving data, such as data streams changing during a disease outbreak, are particularly challenging. Data management is further complicated by data being imprecisely identified when used. Public trust in policy decisions resulting from such analyses is easily damaged and is often low, with cynicism arising where claims of "following the science" are made without accompanying evidence. Tracing the provenance of such decisions back through open software to primary data would clarify this evidence, enhancing the transparency of the decision-making process. Here, we demonstrate a Findable, Accessible, Interoperable and Reusable (FAIR) data pipeline developed during the COVID-19 pandemic that allows easy annotation of data as they are consumed by analyses, while tracing the provenance of scientific outputs back through the analytical source code to data sources. Such a tool provides a mechanism for the public, and fellow scientists, to better assess the trust that should be placed in scientific evidence, while allowing scientists to support policy-makers in openly justifying their decisions. We believe that tools such as this should be promoted for use across all areas of policy-facing research

In Vivo Evaluation of the Presence of Bone Marrow in Cortical Porosity in Postmenopausal Osteopenic Women

This is the first observational study examining cortical porosity in vivo in postmenopausal osteopenic women and to incorporate data from two different imaging modalities to further examine the nature of cortical porosity. The goal of this study was to combine high-resolution peripheral computed tomography (HR-pQCT) images, which contain high spatial resolution information of the cortical structure, and magnetic resonance (MR) images, which allow the visualization of soft tissues such as bone marrow, to observe the amount of cortical porosity that contains bone marrow in postmenopausal osteopenic women. The radius of 49 and the tibia of 51 postmenopausal osteopenic women (age 56 ± 3.7) were scanned using both HR-pQCT and MR imaging. A normalized mutual information registration algorithm was used to obtain a three-dimensional rigid transform which aligned the MR image to the HR-pQCT image. The aligned images allowed for the visualization of bone marrow in cortical pores. From the HR-pQCT image, the percent cortical porosity, the number of cortical pores, and the size of each cortical pore was determined. By overlaying the aligned MR and HR-pQCT images, the percent of cortical pores containing marrow, the number of cortical pores containing marrow, and the size of each cortical pore containing marrow were measured. While the amount of cortical porosity did not vary greatly between subjects, the type of cortical pore, containing marrow vs. not containing marrow, varied highly between subjects. The results suggest that cortical pore spaces contain components of varying composition, and that there may be more than one mechanism for the development of cortical porosity