Highly Variable Objects in the Palomar-QUEST Survey: A Blazar Search using Optical Variability

We identify 3,113 highly variable objects in 7,200 square degrees of the Palomar-QUEST Survey, which each varied by more than 0.4 magnitudes simultaneously in two broadband optical filters on timescales from hours to roughly 3.5 years. The primary goal of the selection is to find blazars by their well-known violent optical variability. Because most known blazars have been found in radio and/or X-ray wavelengths, a sample discovered through optical variability may have very different selection effects, elucidating the range of behavior possible in these systems. A set of blazars selected in this unusual manner will improve our understanding of the physics behind this extremely variable and diverse class of AGN. The object positions, variability statistics, and color information are available using the Palomar-QUEST CasJobs server. The time domain is just beginning to be explored over large sky areas; we do not know exactly what a violently variable sample will hold. About 20% of the sample has been classified in the literature; over 70% of those objects are known or likely AGN. The remainder largely consists of a variety of variable stars, including a number of RR Lyrae and cataclysmic variables.Comment: 22 pages (preprint format), 2 figures. Accepted for publication in ApJ. References update

Placental 11-Beta Hydroxysteroid Dehydrogenase Methylation Is Associated with Newborn Growth and a Measure of Neurobehavioral Outcome

Background: There is growing evidence that the intrauterine environment can impact the neurodevelopment of the fetus through alterations in the functional epigenome of the placenta. In the placenta, the HSD11B2 gene encoding the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol, is regulated by DNA methylation, and has been shown to be susceptible to stressors from the maternal environment. Methodology/Principal Findings: We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 185 healthy newborn infants and infant and maternal characteristics, as well as the association between this epigenetic variability and newborn neurobehavioral outcome assessed with the NICU Network Neurobehavioral Scales. Controlling for confounders, HSD11B2 methylation extent is greatest in infants with the lowest birthweights (P = 0.04), and this increasing methylation was associated with reduced scores of quality of movement (P = 0.04). Conclusions/Significance: These results suggest that factors in the intrauterine environment which contribute to birth outcome may be associated with placental methylation of the HSD11B2 gene and that this epigenetic alteration is in turn associated with a prospectively predictive early neurobehavioral outcome, suggesting in some part a mechanism for th

An Expanded Set of Amino Acid Analogs for the Ribosomal Translation of Unnatural Peptides

BACKGROUND: The application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. The specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. We have previously shown that over 90 unnatural amino acids can be enzymatically loaded onto tRNA. METHODOLOGY/PRINCIPAL FINDINGS: We have now used a competition assay to assess the efficiency of tRNA-aminoacylation of these analogs. We have also used a series of peptide translation assays to measure the efficiency with which these analogs are incorporated into peptides. The translation apparatus tolerates most side chain derivatives, a few alpha,alpha disubstituted, N-methyl and alpha-hydroxy derivatives, but no beta-amino acids. We show that over 50 unnatural amino acids can be incorporated into peptides by ribosomal translation. Using a set of analogs that are efficiently charged and translated we were able to prepare individual peptides containing up to 13 different unnatural amino acids. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that a diverse array of unnatural building blocks can be translationally incorporated into peptides. These building blocks provide new opportunities for in vitro selections with highly modified drug-like peptides

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses

Article Commentary: Online Learning Tools as Supplements for Basic and Clinical Science Education

Undergraduate medical educators are increasingly incorporating online learning tools into basic and clinical science curricula. In this paper, we explore the diversity of online learning tools and consider the range of applications for these tools in classroom and bedside learning. Particular advantages of these tools are highlighted, such as delivering foundational knowledge as part of the “flipped classroom” pedagogy and for depicting unusual physical examination findings and advanced clinical communication skills. With accelerated use of online learning, educators and administrators need to consider pedagogic and practical challenges posed by integrating online learning into individual learning activities, courses, and curricula as a whole. We discuss strategies for faculty development and the role of school-wide resources for supporting and using online learning. Finally, we consider the role of online learning in interprofessional, integrated, and competency-based applications among other contemporary trends in medical education are considered