Improvements in ERBS attitude determination without gyros

Previous papers have described the modification of the Earth Radiation Budget Satellite (ERBS) Attitude Determination System (ADS) to overcome the impact of on board gyro degradation and failure on attitude ground support of the mission. Two approaches were taken: implementing a Kalman filter in place of the batch-least-squares attitude estimator to account for the propagation error produced by high-noise gyro data, and modeling the ERBS attitude dynamics to restore rate information in the case of gyro failure. Both of these methods had shortcomings. In practice, the filter attitude diverged without complete sensor observability, and accurate dynamics modeling required knowledge of disturbance torque parameters that had to be determined manually. These difficulties have been overcome by improved tuning of the filter and by incorporating dynamics parameter estimation into the ERBS ADS

Development of a protocol for maintaining viability while shipping organoid-derived retinal tissue.

Retinal organoid technology enables generation of an inexhaustible supply of three-dimensional retinal tissue from human pluripotent stem cells (hPSCs) for regenerative medicine applications. The high similarity of organoid-derived retinal tissue and transplantable human fetal retina provides an opportunity for evaluating and modeling retinal tissue replacement strategies in relevant animal models in the effort to develop a functional retinal patch to restore vision in patients with profound blindness caused by retinal degeneration. Because of the complexity of this very promising approach requiring specialized stem cell and grafting techniques, the tasks of retinal tissue derivation and transplantation are frequently split between geographically distant teams. Delivery of delicate and perishable neural tissue such as retina to the surgical sites requires a reliable shipping protocol and also controlled temperature conditions with damage-reporting mechanisms in place to prevent transplantation of tissue damaged in transit into expensive animal models. We have developed a robust overnight tissue shipping protocol providing reliable temperature control, live monitoring of the shipment conditions and physical location of the package, and damage reporting at the time of delivery. This allows for shipping of viable (transplantation-competent) hPSC-derived retinal tissue over large distances, thus enabling stem cell and surgical teams from different parts of the country to work together and maximize successful engraftment of organoid-derived retinal tissue. Although this protocol was developed for preclinical in vivo studies in animal models, it is potentially translatable for clinical transplantation in the future and will contribute to developing clinical protocols for restoring vision in patients with retinal degeneration

High-fidelity state detection and tomography of a single ion Zeeman qubit

We demonstrate high-fidelity Zeeman qubit state detection in a single trapped 88 Sr+ ion. Qubit readout is performed by shelving one of the qubit states to a metastable level using a narrow linewidth diode laser at 674 nm followed by state-selective fluorescence detection. The average fidelity reached for the readout of the qubit state is 0.9989(1). We then measure the fidelity of state tomography, averaged over all possible single-qubit states, which is 0.9979(2). We also fully characterize the detection process using quantum process tomography. This readout fidelity is compatible with recent estimates of the detection error-threshold required for fault-tolerant computation, whereas high-fidelity state tomography opens the way for high-precision quantum process tomography

A core genetic module : the Mixed Feedback Loop

The so-called Mixed Feedback Loop (MFL) is a small two-gene network where protein A regulates the transcription of protein B and the two proteins form a heterodimer. It has been found to be statistically over-represented in statistical analyses of gene and protein interaction databases and to lie at the core of several computer-generated genetic networks. Here, we propose and mathematically study a model of the MFL and show that, by itself, it can serve both as a bistable switch and as a clock (an oscillator) depending on kinetic parameters. The MFL phase diagram as well as a detailed description of the nonlinear oscillation regime are presented and some biological examples are discussed. The results emphasize the role of protein interactions in the function of genetic modules and the usefulness of modelling RNA dynamics explicitly.Comment: To be published in Physical Review

Proteasome Lid Bridges Mitochondrial Stress with Cdc53/Cullin1 NEDDylation Status

Cycles of Cdc53/Cullin1 rubylation (a.k.a NEDDylation) protect ubiquitin-E3 SCF (Skp1-Cullin1-F-box protein) complexes from self-destruction and play an important role in mediating the ubiquitination of key protein substrates involved in cell cycle progression, development, and survival. Cul1 rubylation is balanced by the COP9 signalosome (CSN), a multi-subunit derubylase that shows 1:1 paralogy to the 26 S proteasome lid. The turnover of SCF substrates and their relevance to various diseases is well studied, yet, the extent by which environmental perturbations influence Cul1 rubylation/derubylation cycles per se is still unclear. In this study, we show that the level of cellular oxidation serves as a molecular switch, determining Cullin1 rubylation/derubylation ratio. We describe a mutant of the proteasome lid subunit, Rpn11 that exhibits accumulated levels of Cullin1-Rub1 conjugates, a characteristic phenotype of csn mutants. By dissecting between distinct phenotypes of rpn11 mutants, proteasome and mitochondria dysfunction, we were able to recognize the high reactive oxygen species (ROS) production during the transition of cells into mitochondrial respiration, as a checkpoint of Cullin1 rubylation in a reversible manner. Thus, the study adds the rubylation cascade to the list of cellular pathways regulated by redox homeostasis

Genome-wide mapping of the distribution of CarD, RNAP σA, and RNAP β on the Mycobacterium smegmatis chromosome using chromatin immunoprecipitation sequencing

CarD is an essential mycobacterial protein that binds the RNA polymerase (RNAP) and affects the transcriptional profile of Mycobacterium smegmatis and Mycobacterium tuberculosis [6]. We predicted that CarD was directly regulating RNAP function but our prior experiments had not determined at what stage of transcription CarD was functioning and at which genes CarD interacted with the RNAP. To begin to address these open questions, we performed chromatin immunoprecipitation sequencing (ChIP-seq) to survey the distribution of CarD throughout the M. smegmatis chromosome. The distribution of RNAP subunits β and σA were also profiled. We expected that RNAP β would be present throughout transcribed regions and RNAP σA would be predominantly enriched at promoters based on work in Escherichia coli [3], however this had yet to be determined in mycobacteria. The ChIP-seq analyses revealed that CarD was never present on the genome in the absence of RNAP, was primarily associated with promoter regions, and was highly correlated with the distribution of RNAP σA. The colocalization of σA and CarD led us to propose that in vivo, CarD associates with RNAP initiation complexes at most promoters and is therefore a global regulator of transcription initiation. Here we describe in detail the data from the ChIP-seq experiments associated with the study published by Srivastava and colleagues in the Proceedings of the National Academy of Science in 2013 [5] as well as discuss the findings from this dataset in relation to both CarD and mycobacterial transcription as a whole. The ChIP-seq data have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE48164)

Are Patients With Longer Emergency Department Wait Times Less Likely to Consent to Research?

Objectives: There are unique challenges to enrolling patients in emergency department (ED) clinical research studies, including the time-sensitive nature of emergency conditions, the acute care environ- ment, and the lack of an established relationship with patients. Prolonged ED wait times have been asso- ciated with a variety of adverse effects on patient care. The objective of this study was to assess the effect of ED wait times on patient participation in ED clinical research. The hypothesis was that increased ED wait times would be associated with reduced ED clinical research consent rates. Methods: This was a retrospective cohort study of all patients eligible for two diagnostic clinical research studies from January 1, 2008, through December 31, 2008, in an urban academic ED. Sex, age, race, study eligibility, and research consent decisions were recorded by trained study personnel. The wait times to registration and to be seen by a physician were obtained from administrative databases and compared between consenters and nonconsenters. An analysis of association between patient wait times for the outcome of consent to participate was performed using a multivariate logistic regression model. Results: A total of 903 patients were eligible for enrollment and were asked for consent. Overall, 589 eligible patients (65%) gave consent to research participation. The consent rates did not change when patients were stratified by the highest and lowest quartile wait times for both time from arrival to regis- tration (68% vs. 65%, p = 0.35) and time to be seen by a physician (65% vs. 66%, p = 0.58). After adjusting for patient demographics (age, race, and sex) and study, there was still no relationship between wait times and consent (p > 0.4 for both wait times). Furthermore, median time from arrival to registration did not differ between those who consented to participate (15 minutes; interquartile range [IQR] = 9 to 36 minutes) versus those who did not (15.5 minutes; IQR = 10 to 39 minutes; p = 0.80; odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.99 to 1.01). Similarly, there was no difference in the median time to be seen by a physician between those who consented (25 minutes; IQR = 15 to 55 minutes) versus those who did not (25 minutes; IQR = 15 to 56 minutes; p = 0.70; OR = 1.00, 95% CI = 0.99 to 1.01). Conclusions: Regardless of wait times, nearly two-thirds of eligible patients were willing to consent to diagnostic research studies in the ED. These findings suggest that effective enrollment in clinical research is possible in the ED, despite challenges with prolonged wait times

Quantum control of 88^{88}Sr+^+ in a miniature linear Paul trap

We report on the construction and characterization of an apparatus for quantum information experiments using $^{88}$Sr$^+$ ions. A miniature linear radio-frequency (rf) Paul trap was designed and built. Trap frequencies above 1 MHz in all directions are obtained with 50 V on the trap end-caps and less than 1 W of rf power. We encode a quantum bit (qubit) in the two spin states of the $S_{1/2}$ electronic ground-state of the ion. We constructed all the necessary laser sources for laser cooling and full coherent manipulation of the ions' external and internal states. Oscillating magnetic fields are used for coherent spin rotations. High-fidelity readout as well as a coherence time of 2.5 ms are demonstrated. Following resolved sideband cooling the average axial vibrational quanta of a single trapped ion is $\bar n=0.05$ and a heating rate of $\dot{\bar n}=0.016$ ms$^{-1}$ is measured.Comment: 8 pages,9 figure

Sensitivity of the human circadian system to short wavelength (420 nm) light

The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment, melanopsin. Nine action spectrum studies using rodents, monkeys, and human for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 nm to 484 nm, with some disagreement in short wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420 nm light for plasma melatonin suppression. Adult female (N=14) and male (N=12) subjects participated in two studies, each employing a within-subjects design. In a fluence-response study, subjects (N=8) were tested with eight light irradiances at 420 nm ranging over a four log unit photon density range of 1010 to 1014 photons/cm2/sec and one dark exposure control night. In the other study, subjects (N=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 1013 photons/cm2/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420 nm light and melatonin suppression (p\u3c0.001) with a half-saturation constant of 2.74 x 1011 photons/cm2/sec. The second study showed that 460 nm light is significantly stronger than 420 nm light for suppressing melatonin (p\u3c0.04). Together, the results clarify the visible short wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications