Titanium Nitride Films for Ultrasensitive Microresonator Detectors

Titanium nitride (TiNx) films are ideal for use in superconducting microresonator detectors because: a) the critical temperature varies with composition (0 < Tc < 5 K); b) the normal-state resistivity is large, \rho_n ~ 100 $\mu$Ohm cm, facilitating efficient photon absorption and providing a large kinetic inductance and detector responsivity; and c) TiN films are very hard and mechanically robust. Resonators using reactively sputtered TiN films show remarkably low loss (Q_i > 10^7) and have noise properties similar to resonators made using other materials, while the quasiparticle lifetimes are reasonably long, 10-200 $\mu$s. TiN microresonators should therefore reach sensitivities well below 10^-19 WHz^(-1/2).Comment: to be published in AP

Understanding Schools and Schooling. (Book Review)

A review of a book written by Clive Chitty (2002 with a useful focus on issues of equity and social justice, including prejudice, discrimination and bullying in secondary schools. Education policy makers need to explore the extent to which it is important to produce interested, motivated and socially balanced young adults. It is well researched and documented

Extraordinary Late-Time Infrared Emission of Type IIn Supernovae

Near-Infrared (NIR) observations are presented for five Type IIn supernovae (SN 1995N, SN 1997ab, SN 1998S, SN 1999Z, and SN 1999el) that exhibit strong infrared excesses at late times (t >= 100 d). H- and K-band emission from these objects is dominated by a continuum that rises toward longer wavelengths. The data are interpreted as thermal emission from dust, probably situated in a pre-existing circumstellar nebula. The IR luminosities implied by single temperature blackbody fits are quite large,> 10^(41 - 42) erg s^-1, and the emission evolves slowly, lasting for years after maximum light. For SN 1995N, the integrated energy release via IR dust emission was 0.5 -- 1 * 10^50 erg. A number of dust heating scenarios are considered, the most likely being an infrared echo poweredby X-ray and UV emissions from the shock interaction with a dense circumstellar medium.Comment: 14 Pages, 3 Figures, Accecpted for publication in The Astrophysical Journa

Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis

AbstractTransthyretin amyloidosis is a fatal disorder that is characterized primarily by progressive neuropathy and cardiomyopathy. It occurs in both a mutant form (with autosomal dominant inheritance) and a wild-type form (with predominant cardiac involvement). This article guides clinicians as to when the disease should be suspected, describes the appropriate diagnostic evaluation for those with known or suspected amyloidosis, and reviews the interventions currently available for affected patients

Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/Background: Hereditary transthyretin amyloidosis (hATTR/ATTRv) results from the deposition of misfolded transthyretin (TTR) throughout the body, including peripheral nerves. Inotersen, an antisense oligonucleotide inhibitor of hepatic TTR production, demonstrated a favorable efficacy and safety profile in patients with the polyneuropathy associated with hATTR in the NEURO-TTR (NCT01737398) study. We report longer-term efficacy and safety data for inotersen, with a median treatment exposure of 3 years. Methods: Patients who satisfactorily completed NEURO-TTR were enrolled in its open-label extension (OLE) study. Efficacy assessments included the modified Neuropathy Impairment Score + 7 (mNIS + 7), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) questionnaire total score, and the Short Form 36 (SF-36v2) Health Survey Physical Component Summary score. Safety and tolerability were also assessed. Efficacy is reported for patients living in Europe and North America (this cohort completed the study approximately 9 months before the remaining group of patients outside these regions); safety is reported for the full safety dataset, comprising patients living in Europe, North America, and Latin America/Australasia. This study is registered with ClinicalTrials.gov, identifier NCT02175004. Results: In the Europe and North America cohort of the NEURO-TTR study, 113/141 patients (80.1%) completed the study, and 109 patients participated in the OLE study. A total of 70 patients continued to receive inotersen (inotersen-inotersen) and 39 switched from placebo to inotersen (placebo-inotersen). The placebo-inotersen group demonstrated sustained improvement in neurological disease progression as measured by mNIS + 7, compared with predicted worsening based on projection of the NEURO-TTR placebo data (estimated natural history). The inotersen-inotersen group demonstrated sustained benefit, as measured by mNIS + 7, Norfolk QoL-DN, and SF-36v2, compared with estimated natural history as well as compared with the placebo-inotersen group. With a maximum exposure of 6.2 years, inotersen was not associated with any additional safety concerns or increased toxicity in the OLE study. Platelet and renal monitoring were effective in reducing the risk of severe adverse events in the OLE study. Conclusion: Inotersen treatment for > 3 years slowed progression of the polyneuropathy associated with hATTR, and no new safety signals were observed.info:eu-repo/semantics/publishedVersio

Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial

Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations.Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis.Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed.Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity.Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems

Towards an Intelligent Tutor for Mathematical Proofs

Computer-supported learning is an increasingly important form of study since it allows for independent learning and individualized instruction. In this paper, we discuss a novel approach to developing an intelligent tutoring system for teaching textbook-style mathematical proofs. We characterize the particularities of the domain and discuss common ITS design models. Our approach is motivated by phenomena found in a corpus of tutorial dialogs that were collected in a Wizard-of-Oz experiment. We show how an intelligent tutor for textbook-style mathematical proofs can be built on top of an adapted assertion-level proof assistant by reusing representations and proof search strategies originally developed for automated and interactive theorem proving. The resulting prototype was successfully evaluated on a corpus of tutorial dialogs and yields good results.Comment: In Proceedings THedu'11, arXiv:1202.453

Dimorphos's Orbit Period Change and Attitude Perturbation due to Its Reshaping after the DART Impact

On 2022 September 26 (UTC), NASA's Double Asteroid Redirection Test (DART) mission achieved a successful impact on Dimorphos, the secondary component of the near-Earth binary asteroid system (65803) Didymos. Subsequent ground-based observations suggest a significant reshaping of Dimorphos, with its equatorial axis ratio changing from 1.06 to ∼1.3. Here we report the effects of this reshaping event on Dimorphos's orbit and attitude. Given the reported reshaping magnitude, our mutual dynamics simulations show that approximately 125 s of the observed 33 minute orbit period change after the DART impact may have resulted from reshaping. This value, however, is sensitive to the precise values of Dimorphos's post-impact axis ratios and may vary by up to 2 times that amount, reaching approximately 250 s within the current uncertainty range. While the rotational state of the body is stable at the currently estimated axis ratios, even minor changes in these ratios or the introduction of shape asymmetry can render its attitude unstable. The perturbation to Dimorphos's orbital and rotational state delivered by the impact directly, combined with any reshaping, leads to a strong possibility for a tumbling rotation state. To accurately determine the momentum enhancement factor (β) through measurements by the European Space Agency's Hera spacecraft and to evaluate the effectiveness of the kinetic deflection technique for future planetary defense initiatives, the effects of reshaping should not be overlooked.This work was supported in part by the DART mission, NASA contract 80MSFC20D0004 to JHU/APL. R.N. acknowledges support from NASA/FINESST (NNH20ZDA001N). S.D.R. and M.J. acknowledge support from the Swiss National Science Foundation (project number 200021_207359). P.M. acknowledges funding support from the French Space Agency CNES and The University of Tokyo. P.P. acknowledges support from the grant Agency of the Czech Republic, grant 23-04946S. S.R.S. acknowledges support from the DART Participating Scientist Program, grant No. 80NSSC22K0318. A.C.B. and P.Y.L. acknowledge funding by the NEO-MAPP project 717 GA 870377, EC H2020-SPACE-718 2018-2020/H2020-SPACE-2019, and by MICINN (Spain) PGC2021, PID2021-125883NB-C21. P.Y.L. acknowledges funding from the European Space Agency OSIP contract N.4000136043/21/NL/GLC/my. A portion of this work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (No. 80NM0018D0004)