The Palomar Kernel Phase Experiment: Testing Kernel Phase Interferometry for Ground-based Astronomical Observations

At present, the principal limitation on the resolution and contrast of astronomical imaging instruments comes from aberrations in the optical path, which may be imposed by the Earth's turbulent atmosphere or by variations in the alignment and shape of the telescope optics. These errors can be corrected physically, with active and adaptive optics, and in post-processing of the resulting image. A recently-developed adaptive optics post-processing technique, called kernel phase interferometry, uses linear combinations of phases that are self-calibrating with respect to small errors, with the goal of constructing observables that are robust against the residual optical aberrations in otherwise well-corrected imaging systems. Here we present a direct comparison between kernel phase and the more established competing techniques, aperture masking interferometry, point spread function (PSF) fitting and bispectral analysis. We resolve the alpha Ophiuchi binary system near periastron, using the Palomar 200-Inch Telescope. This is the first case in which kernel phase has been used with a full aperture to resolve a system close to the diffraction limit with ground-based extreme adaptive optics observations. Excellent agreement in astrometric quantities is found between kernel phase and masking, and kernel phase significantly outperforms PSF fitting and bispectral analysis, demonstrating its viability as an alternative to conventional non-redundant masking under appropriate conditions.Comment: Accepted to MNRA

Crosstalk and the evolvability of intracellular communication

Metazoan signalling networks are complex, with extensive crosstalk between pathways. It is unclear what pressures drove the evolution of this architecture. We explore the hypothesis that crosstalk allows different cell types, each expressing a specific subset of signalling proteins, to activate different outputs when faced with the same inputs, responding differently to the same environment. We find that the pressure to generate diversity leads to the evolution of networks with extensive crosstalk. Using available data, we find that human tissues exhibit higher levels of diversity between cell types than networks with random expression patterns or networks with no crosstalk. We also find that crosstalk and differential expression can influence drug activity: no protein has the same impact on two tissues when inhibited. In addition to providing a possible explanation for the evolution of crosstalk, our work indicates that consideration of cellular context will likely be crucial for targeting signalling networks

Hepatitis B surface antigen in urine of hemodialysis patients

Hepatitis B surface antigen in urine of hemodialysis patients. As part of an extensive epidemiological survey of chronic hemodialysis patients in Michigan, hepatitis B surface antigen (HBsAg) was identified in the sera of 79 of 701 (11%) patients. Of these patients, 59 were carriers of HBsAg for three or more months. Urine samples were collected from 36 of 39 HBsAg carriers having urinary output. Of these samples, 19 (52%) were positive for HBsAg by radioimmunoassay; this was confirmed by specific antibody neutralization. The HBsAg was not identified in the urine of seven hemodialysis patients who were lacking serum HBsAg or in urine samples from three HBsAg sero-carriers who had normal renal function. Patients undergoing maintenance hemodialysis appear to constitute a large reservoir of HBsAg chronic carriers. This study indicates that a minimum of 50% of persistent HBsAg carriers who are producing urine have detectable. HBsAg in single, randomly timed, unconcentrated urine specimen. These data suggest that urine may represent a potential vehicle for transmission in nonparenterally acquired hepatitis B.Antigène de surface de l'hépatite B dans l'urine de malades en hémodialyse. Dans le cadre d'une large enquête épidémiologique à propos des malades en hémodialyse chronique dans le Michigan, l'antigène de surface de l'hépatite B (HBsAg) a été identifié dans le sérum de 79 parmi 701 malades (11%). Parmi ces malades, 59 étaient des porteurs de HBsAg depuis 3 mois ou plus. L'urine de 36 des 39 porteurs de HBsAg, qui avaient une diurèse, a été recueillie. Parmi ces 36 urines, 19 (52%) sont positives pour HBsAg par radio-immunologie, ce qui est confirmé par la neutralisation au moyen d'anticorps spécifique. Le HBsAg n'apas été identifié dans l'urine de 7 malades en hémodialyse qui n'avaient pas le HBsAg sérique et dans l'urine de 3 porteurs de HBsAg dont les fonctions rénales étaient normales. Les malades soumis à l'hémodialyse itérative paraissent constituer un grand réservoir de porteurs chroniques de HBsAg. Cette étude indique qu'au minimum 50% des porteurs chroniques de HBsAg qui ont une diurèse, ont un HBsAg détectable dans un échantillon unique d'urine, prélevé au hasard, non concentré. Ces résultats suggèrent que l'urine peut être un véhicule de transmission de l'hépatite B acquise par voie non parentérale

Efficacy and Safety of SHP465 Mixed Amphetamine Salts in the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults: Results of a Randomized, Double-Blind, Placebo-Controlled, Forced-Dose Clinical Study

OBJECTIVE: The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and safety of SHP465 mixed amphetamine salts (MAS) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Eligible adults [aged 18-55 years; meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ADHD criteria; baseline ADHD Rating Scale with Adult Prompts (ADHD-RS-AP) total scores ≥28] were randomized 1:1:1 to placebo or forced-dose SHP465 MAS (12.5 or 37.5 mg/day) for 4 weeks. The ADHD-RS-AP total score change from baseline to week 4 (primary endpoint) and Clinical Global Impressions-Improvement score at week 4 (key secondary endpoint) were assessed using linear mixed-effects models for repeated measures. Other efficacy endpoints were changes from baseline to week 4 on the ADHD-RS-AP hyperactivity/impulsivity and inattentiveness subscales and the percentage of participants categorized as improved on the dichotomized Clinical Global Impressions-Improvement. Safety and tolerability assessments were treatment-emergent adverse events, vital sign and weight changes, Columbia-Suicide Severity Rating Scale responses, and electrocardiogram results. RESULTS: Of 369 screened participants, 275 were randomized (placebo, n = 91; 12.5 mg/day of SHP465 MAS, n = 92; 37.5 mg/day of SHP465 MAS, n = 92) and 236 completed the study (placebo, n = 80; 12.5 mg/day of SHP465 MAS, n = 80; 37.5 mg/day of SHP465 MAS, n = 76). Least-squares mean (95% confidence interval) treatment differences at week 4 significantly favored SHP465 MAS over placebo for the ADHD-RS-AP total score change from baseline [12.5 mg/day: -8.1 (-11.7, -4.4), effect size = 0.67; 37.5 mg/day: -13.4 (-17.1, -9.7), effect size = 1.11; both p 5%) with SHP465 MAS were decreased appetite, dry mouth, insomnia, headache, anxiety, initial insomnia, irritability, and bruxism. Severe treatment-emergent adverse events and treatment-emergent adverse events leading to discontinuation, respectively, were reported by 8 and 12 participants (placebo, n = 2 and 0; 12.5 mg/day SHP465 MAS, n = 1 and 7; 37.5 mg/day SHP465 MAS, n = 5 and 5). At the final on-treatment assessment, mean ± standard deviation increases from baseline were observed with 12.5 and 37.5 mg/day of SHP465 MAS for pulse (3.3 ± 10.52 and 7.1 ± 11.48 bpm) and blood pressure (systolic 0.2 ± 7.24 and 1.7 ± 9.99 mmHg; diastolic 1.0 ± 7.46 and 2.8 ± 7.90 mmHg) and decreases were observed for weight (-0.97 ± 1.523 and -1.65 ± 2.333 kg), body mass index (-0.33 ± 0.519 and -0.56 ± 0.777 kg/m2), and Fridericia corrected QT interval (-3.0 ± 10.72 and -1.6 ± 13.70 ms). No participant in any treatment group had a positive response for on-study Columbia-Suicide Severity Rating Scale assessments. CONCLUSIONS: SHP465 MAS was superior to placebo in reducing ADHD symptoms, with a safety profile consistent with other long-acting stimulants. ClinicalTrials.gov Registry Number: NCT02604407

Recombinant human preproinsulin expression, purification and reaction with insulin autoantibodies in sera from patients with insulin-dependent diabetes mellitus

A novel prokaryotic expression vector pGEX-6T was designed for high-level expression of recombinant fusion protein with a histidine-hexapeptide and glutathione-S-transferase at its N-terminus and the recombinant human preproinsulin at its C-terminus. Efficiency of expression was investigated in the Escherichia coli strain CAG456. The synthesized protein was sequestered in an insoluble form in inclusion bodies and was purified to homogeneity by one-step affinity chromatography based on the specific complex formation of the histidine-hexapeptide and a chelating matrix which was charged with Ni2+ ions. The antigenic nature of the purified recombinant preproinsulin fusion protein was evaluated by ELISA screening for insulin autoantibodies in selected sera from patients with recent-onset type 1 (insulin-dependent) diabetes mellitus classified by the existence of additional autoantibodies reactive against glutamic acid decarboxylase. 14% of the tested sera (n=43) conttained insulin autoantibodies which strongly recognized the recombinant human preproinsulin. Comparable measurements with both recombinant human preproinsulin and mature insulin suggested that the observed autoantigenicity of preproinsulin was mediated by the C-peptide or/and signal peptide

The Palomar kernel-phase experiment: testing kernel phase interferometry for ground-based astronomical observations

At present, the principal limitation on the resolution and contrast of astronomical imaging instruments comes from aberrations in the optical path, which may be imposed by the Earth's turbulent atmosphere or by variations in the alignment and shape of the telescope optics. These errors can be corrected physically,with active and adaptive optics, and in post-processing of the resulting image.Arecently developed adaptive optics post-processing technique, called kernelphase interferometry, uses linear combinations of phases that are self-calibrating with respect to small errors, with the goal of constructing observables that are robust against the residual optical aberrations in otherwise well-corrected imaging systems. Here, we present a direct comparison between kernel phase and the more established competing techniques, aperture masking interferometry, point spread function (PSF) fitting and bispectral analysis.We resolve the α Ophiuchi binary system near periastron, using the Palomar 200-Inch Telescope. This is the first case in which kernel phase has been used with a full aperture to resolve a system close to the diffraction limit with ground-based extreme adaptive optics observations. Excellent agreement in astrometric quantities is found between kernel phase and masking, and kernel phase significantly outperforms PSF fitting and bispectral analysis, demonstrating its viability as an alternative to conventional non-redundant masking under appropriate conditions