Satellite applications to marine geodesy

Potential use of satellites for enhancing positioning capabilities and for marine geodetic contro

An Engineered Glutamate-gated Chloride (GluCl) Channel for Sensitive, Consistent Neuronal Silencing by Ivermectin

A modified invertebrate glutamate-gated Cl− channel (GluCl αβ) was previously employed to allow pharmacologically induced silencing of electrical activity in CNS neurons upon exposure to the anthelmintic drug ivermectin (IVM). Usefulness of the previous receptor was limited by 1) the high concentration of IVM necessary to elicit a consistent silencing phenotype, raising concern about potential side effects, and 2) the variable extent of neuronal spike suppression, due to variations in the co-expression levels of the fluorescent protein-tagged α and β subunits. To address these issues, mutant receptors generated via rational protein engineering strategies were examined for improvement. Introduction of a gain-of-function mutation (L9′F) in the second transmembrane domain of the α subunit appears to facilitate β subunit incorporation and substantially increase heteromeric GluCl αβ sensitivity to IVM. Removal of an arginine-based endoplasmic reticulum retention motif (RSR mutated to AAA) from the intracellular loop of the β subunit further promotes heteromeric expression at the plasma membrane possibly by preventing endoplasmic reticulum-associated degradation of the β subunit rather than simply reducing endoplasmic reticulum retention. A monomeric XFP (mXFP) mutation that prevents fluorescent protein dimerization complements the mutant channel effects. Expression of the newly engineered GluCl opt α-mXFP L9′F + opt β-mXFP Y182F RSR_AAA receptor in dissociated neuronal cultures markedly increases conductance and reduces variability in spike suppression at 1 nm IVM. This receptor, named “GluClv2.0,” is an improved tool for IVM-induced silencing

The Limits of Citizenship: Rights of Prisoners and ex-Prisoners in USA

Contrary to popular beliefs and commonly held rhetoric, rights are not naturally given to people/residents/citizens. Very few, if any, rights are inherently granted by virtue of being born a human being. Although the authors of the Bill of Rights (in the USA) as well as the United Nations Declaration of Human Rights want us to believe that these rights are innate, in fact they were fought for and only barely achieved. At any given time, there are counter forces that actively push to minimize and reverse rights that were gained after long and hard struggles. For example, in the United States the “sacred” right for privacy was vastly violated with the signature and support of President George W. Bush soon after the attack of September 11, 2001 was carried out within the boundaries of the country. This is but one example where rights are not guaranteed forever and are only in place so long as there are enough people actively fighting to keep them and, if possible, to expand them. My argument, though my data are mostly US-based, is that the rights of prisoners and ex-prisoners are an excellent measure and estimate for the strength of human rights in a given society. The more punitive and exclusionary are the policies towards prisoners and ex-prisoners, the less protected are the rights of citizens in general. The more a society excludes prisoners and ex-prisoners, the more ready it is to limit the rights of other members of that society. I would welcome a comparative study of this topic to assess which societies treat prisoners and ex-prisoners more humanly and which in a more exclusionary manner

Data Citation in Neuroimaging: Proposed Best Practices for Data Identification and Attribution

Data sharing and reuse, while widely accepted as good ideas, have been slow to catch on in any concrete and consistent way. One major hurdle within the scientific community has been the lack of widely accepted standards for citing that data, making it difficult to track usage and measure impact. Within the neuroimaging community, there is a need for a way to not only clearly identify and cite datasets, but also to derive new aggregate sets from multiple sources while clearly maintaining lines of attribution. This work presents a functional prototype of a system to integrate Digital Object Identifiers (DOI) and a standardized metadata schema into a XNAT-based repository workflow, allowing for identification of data at both the project and image level. These item and source level identifiers allow any newly defined combination of images, from any number of projects, to be tagged with a new group-level DOI that automatically inherits the individual attributes and provenance information of its constituent parts. This system enables the tracking of data reuse down to the level of individual images. The implementation of this type of data identification system would impact researchers and data creators, data hosting facilities, and data publishers, but the benefit of having widely accepted standards for data identification and attribution would go far toward making data citation practical and advantageous

CANDI Store: An Infrastructure for Neuroimage Storage and Processing

In order to support the local data management need for neuroimaging researchers at UMass Medical School within the Child and Adolescent NeuroDevelopment Initiative (CANDI) and beyond, we have implemented a XNAT (xnat.org) instance called CANDIStore. XNAT is an open source imaging informatics platform, developed by the Neuroinformatics Research Group at Washington University. It facilitates common management, productivity, and quality assurance tasks for imaging and associated data. Located securely within the medical school firewall, CANDIStore offers a comprehensive set of image management tools. Users can be authenticated based against their UMass credentials, create private projects, manage research team access, DICOM \u27push\u27 directly to CANDIStore from the MRI imaging console, manage demographic and additional subject variables, and perform automated analysis and processing pipelines. CANDIStore is an essential adjunct to the daily operations of neuroimaging research

An assessment of the autism neuroimaging literature for the prospects of re-executability

Background: The degree of reproducibility of the neuroimaging literature in psychiatric application areas has been called into question and the issues that relate to this reproducibility are extremely complex. Some of these complexities have to do with the underlying biology of the disorders that we study and others arise due to the technology we apply to the analysis of the data we collect. Ultimately, the observations we make get communicated to the rest of the community through publications in the scientific literature. Methods: We sought to perform a ‘re-executability survey’ to evaluate the recent neuroimaging literature with an eye toward seeing if the technical aspects of our publication practices are helping or hindering the overall quest for a more reproducible understanding of brain development and aging. The topic areas examined include availability of the data, the precision of the imaging method description and the reporting of the statistical analytic approach, and the availability of the complete results. We applied the survey to 50 publications in the autism neuroimaging literature that were published between September 16, 2017 to October 1, 2018. Results: The results of the survey indicate that for the literature examined, data that is not already part of a public repository is rarely available, software tools are usually named but versions and operating system are not, it is expected that reasonably skilled analysts could approximately perform the analyses described, and the complete results of the studies are rarely available. Conclusions: We have identified that there is ample room for improvement in research publication practices. We hope exposing these issues in the retrospective literature can provide guidance and motivation for improving this aspect of our reporting practices in the future

Investigating Potential Biomarkers in Autism Spectrum Disorder

Background: Early identification and treatment of individuals with autism spectrum disorder (ASD) improves outcomes, but specific evidence needed to individualize treatment recommendations is lacking. Biomarkers that could be routinely measured within the clinical setting could potentially transform clinical care for patients with ASD. This demonstration project employed collection of biomarker data during regular autism specialty clinical visits and explored the relationship of biomarkers with clinical ASD symptoms. Methods: Eighty-three children with ASD, aged 5-10 years, completed a multi-site feasibility study integrating the collection of biochemical (blood serotonin, urine melatonin sulfate excretion) and clinical (head circumference, dysmorphology exam, digit ratio, cognitive and behavioral function) biomarkers during routine ASD clinic visits. Parents completed a demographic survey and the Aberrant Behavior Checklist-Community. Cognitive function was determined by record review. Data analysis utilized Wilcoxon two-sample tests and Spearman correlations. Results: Participants were 82% male, 63% White, 19% Hispanic, with a broad range of functioning. Group means indicated hyperserotonemia. In a single regression analysis adjusting for race and median household income, higher income was associated with higher levels of blood serotonin and urine melatonin sulfate excretion levels (p = 0.004 and p = 0.04, respectively). Melatonin correlated negatively with age (p = 0.048) and reported neurologic problems (p = 0.02). Dysmorphic status correlated with higher reported stereotyped behavior (p = 0.02) and inappropriate speech (p = 0.04). Conclusion: This demonstration project employed collection of multiple biomarkers, allowed for examination of associations between biochemical and clinical measures, and identified several findings that suggest direction for future studies. This clinical research model has promise for integrative biomarker research in individuals with complex, heterogeneous neurodevelopmental disorders such as ASD

Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families

Abstract Background Previous studies have demonstrated aggregation of autistic traits in undiagnosed family members of children with autism spectrum disorder (ASD), which has significant implications for ASD risk in their offspring. This study capitalizes upon a large, quantitatively characterized clinical-epidemiologic family sample to establish the extent to which family transmission pattern and sex modulate ASD trait aggregation. Methods Data were analyzed from 5515 siblings (2657 non-ASD and 2858 ASD) included in the Interactive Autism Network. Autism symptom levels were measured using the Social Responsiveness Scale (SRS) and by computing Diagnostic and Statistical Manual of Mental Disorders—Fifth Edition (DSM-5) symptom scores based on items from the SRS and Social Communication Questionnaire. Generalized estimating equation models evaluated the influence of family incidence types (single versus multiple incidence families; male-only ASD-affected families versus families with female ASD-affected children), diagnostic group (non-ASD children with and without a history of language delay with autistic speech and ASD-affected children), and sibling sex on ASD symptom levels. Results Non-ASD children manifested elevated ASD symptom burden when they were members of multiple incidence families—this effect was accentuated for male children in female ASD-containing families—or when they had a history of language delay with autistic qualities of speech. In this sample, ASD-affected children from multiple incidence families had lower symptom levels than their counterparts in single incidence families. Recurrence risk for ASD was higher for children from female ASD-containing families than for children from male-only families. Conclusions Sex and patterns of family transmission modulate the risk of autism symptom burden in undiagnosed siblings of ASD-affected children. Identification of these symptoms/traits and their molecular genetic causes may have significant implications for genetic counseling and for understanding inherited liabilities that confer risk for ASD in successive generations. Autism symptom elevations were more dramatic in non-ASD children from multiple incidence families and those with a history of language delay and autistic qualities of speech, identifying sub-groups at substantially greater transmission risk. Higher symptom burden and greater recurrence in children from female ASD-containing families indicate that familial aggregation patterns are further qualified by sex-specific thresholds, supportive of the notion that females require a higher burden of deleterious liability to cross into categorical ASD diagnosis

Psychiatric Symptomatology, Mood Regulation, and Resting State Functional Connectivity of the Amygdala: Preliminary Findings in Youth With Mood Disorders and Childhood Trauma

Background: As mood dysregulation and hyperarousal are overlapping and prominent features of posttraumatic stress disorder (PTSD), and mood disorders (MD) including bipolar disorder (BD), we aimed to clarify the role of trauma and MD on the resting state functional connectivity (RSFC) of amygdala in MD youth with or without trauma exposure, and healthy controls (HC). Methods: Of 23 subjects, 21 completed the magnetic resonance imaging (MRI) protocol, 5 were excluded for subject motion, leaving final sample size of 16: nine subjects with MD (5/9 with trauma), and 7 HC. Youth were assessed with Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL), and other behavioral measures including Young Mania Rating Scale (YMRS). Imaging data were acquired using functional MRI in 3-T scanner. Imaging included T1-weighted structural MRI and 6-min resting state acquisition. Results: In between group analysis, the average correlation coefficients between left anterior cingulate cortex (Acc) and left insula cortex with left amygdala regions were significantly larger in HC compared to the patient population. Connectivity between left amygdala and left cingulate cortex shows a significant negative correlation with YMRS severity. Conclusions: In this preliminary study, MD with trauma youth had more manic symptoms and difficulties regulating anger. While MD youth showed reduced RSFC of left amygdala with left acc and left insula, no significant difference between the subgroups of children with MD was observed. However, when looking at both clinical groups together, we observed a significant correlation of RSFC of left amygdala to left acc, and YMRS scores

Apollo Lightcraft project

The detailed design of a beam-powered transatmospheric vehicle, the Apollo Lightcraft, was selected as the project for the design course. The principal goal is to reduce the LEO payload delivery cost by at least three orders of magnitude below the Space Shuttle Orbiter in the post 2020 era. The completely reusable, single-stage-to-orbit shuttlecraft will take off and land vertically, and have a reentry heat shield integrated with its lower surface. At appropriate points along the launch trajectory, the combined cycle propulsion system will transition through three or four airbreathing modes, and finally use a pure rocket mode for orbital insertion. The objective for the Spring semester propulsion source was to design and perform a detailed theoretical analysis on an advanced combined-cycle engine suitable for the Apollo Lightcraft. The preliminary theoretical analysis of this combined-cycle engine is now completed, and the acceleration performance along representative orbital trajectories was simulated. The total round trip cost is $3430 or$686 per person. This represents a payload delivery cost of $3.11/lb, which is a factor of 1000 below the STS. The Apollo Lightcraft concept is now ready for a more detailed investigation during the Fall semester Transatmosphere Vehicle Design course