Macromolecular recognition: Structural aspects of the origin of the genetic system

Theoretical simulation of prebiotic chemical processes is an invaluable tool for probing the phenomenon of the evolution of life. Using computational and modeling techniques and guided by analogies from present day systems, we seek to understand the emergence of the genetic apparatus, enzymatic catalysis and protein synthesis under prebiotic conditions. Modeling of the ancestral aminoacyl-tRNA-synthetases (aRS) may provide important clues to the emergence of the genetic code and the protein synthetic machinery. The minimal structural requirements for the catalysis of tRNA aminoacylation are being explored. A formation of an aminoacyl adenylate was studied in the framework of ab initio molecular orbital theory. The role of individual residues in the vicinity of the TyrRS active site was examined, and the effect of all possible amino acids substitutions near the active site was examined. A formation of aminoacyl tRNA was studied by the molecular modeling system SYBYL with the high resolution crystallographic structures of the present day tRNA, aRS's complexes. The ultimate goal is to propose a simple RNA segment that is small enough to be build in the primordial chemical environment but maintains the specificity and catalytic activity of the contemporary RNA enzyme. To understand the mechanism of ribozyme catalyzed reactions, ab initio and semi-empirical (ZINDO) programs were used to investigate the reaction path of transphosphorylation. A special emphasis was placed on the possible catalytic and structural roles played by the coordinated magnesium cation. Both the inline and adjacent mechanisms of transphosphorylation were studied. The structural characteristics of the target helices, particularly a possible role for the G-T pair, is also studied by a molecular dynamics (MD) simulation technique

Who Needs Goals? A Case Study of a Goal-Free Evaluation

Background: Goal-free evaluation (GFE) is any evaluation in which the evaluator conducts the evaluation without knowledge of or reference to predetermined goals and objectives whereas the goal-based evaluator determines merit according to the evaluand’s goal achievement. Purpose: To examine a GFE in actual practice focusing on its operationalization as well as paying particular attention to the evaluation users’ perspective of its utility. Setting: The evaluand was a day long training of summer camp counselors on occupational therapy (OT) related skills such as feeding, dressing, and bathing.  Intervention: GFE was the intervention however for comparison purposes an independent and simultaneous goal-based evaluation (GBE) also evaluated the evaluand. Research Design: Case study. Data Collection and Analysis: After the evaluation users read both the GBE and GFE reports, data collection consisted of a semantic differential questionnaires followed by a focus group. Additionally, the research team analyzed both GBE and GFE reports for relevant themes. Findings: The evaluation users reported a slightly more positive attitude toward the GFE report on the semantic differential yet many focus group respondents stated that they found the GBE report more useful or perceived no difference between the two. Evaluation users reported the benefits of GFE to include its potential for developing or aligning goals, expanding the pool of potential outcomes, and supplementing GBE strategies.

The Neuroanatomical Organization of Projection Neurons Associated with Different Olfactory Bulb Pathways in the Sea Lamprey, Petromyzon marinus

Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs) of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb). While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate

Quantum Hall resistance standards from graphene grown by chemical vapor deposition on silicon carbide

Replacing GaAs by graphene to realize more practical quantum Hall resistance standards (QHRS), accurate to within $10^{-9}$ in relative value, but operating at lower magnetic fields than 10 T, is an ongoing goal in metrology. To date, the required accuracy has been reported, only few times, in graphene grown on SiC by sublimation of Si, under higher magnetic fields. Here, we report on a device made of graphene grown by chemical vapour deposition on SiC which demonstrates such accuracies of the Hall resistance from 10 T up to 19 T at 1.4 K. This is explained by a quantum Hall effect with low dissipation, resulting from strongly localized bulk states at the magnetic length scale, over a wide magnetic field range. Our results show that graphene-based QHRS can replace their GaAs counterparts by operating in as-convenient cryomagnetic conditions, but over an extended magnetic field range. They rely on a promising hybrid and scalable growth method and a fabrication process achieving low-electron density devices.Comment: 12 pages, 8 figure

Isopycnic Phases and Structures in H2O/CO2/Ethoxylated Alcohol Surfactant Mixtures

Ternary mixtures of H2O and CO2 with ethoxylated alcohol (C(i)E(j)) surfactants can form three coexisting liquid phases at conditions where two of the phases have the same density (isopycnic phases). Isopycnic phase behavior has been observed for mixtures containing the surfactants C8E5, C10E6, and C12E6, but not for those mixtures containing either C4E1 or CgE3. Pressure-temperature (PT) projections for this isopycnic three-phase equilibrium were determined for H2O/CO2/C8E5 and H2O/CO2/C10E6 mixtures at temperatures from approximately 25 to 33 C and pressures between 90 and 350 bar. As a preliminary to measuring the microstructure in isopycnic three component mixtures, phase behavior and small angle neutron scattering (SANS) experiments were performed on mixtures of D2O/CO2/ n-hexaethyleneglycol monododecyl ether (C12E6) as a function of temperature (25-31 C), pressure (63.1-90.7 bar), and CO2 composition (0-3.9 wt%). Parameters extracted from model fits of the SANS spectra indicate that, while micellar structure remains essentially unchanged, critical concentration fluctuations increase as the phase boundary and plait point are approached

Determination of the eta'-proton scattering length in free space

Taking advantage of both the high mass resolution of the COSY-11 detector and the high energy resolution of the low-emittance proton-beam of the Cooler Synchrotron COSY we determine the excitation function for the pp --> pp eta' reaction close-to-threshold. Combining these data with previous results we extract the scattering length for the eta'-proton potential in free space to be Re(a_{p eta'}) = 0+-0.43 fm and Im(a_{p eta'}) = 0.37(+0.40)(-0.16) fm.Comment: 5 pages, 3 figures, accepted for publication in Phys. Rev. Let

On the segmentation and classification of hand radiographs

This research is part of a wider project to build predictive models of bone age using hand radiograph images. We examine ways of finding the outline of a hand from an X-ray as the first stage in segmenting the image into constituent bones. We assess a variety of algorithms including contouring, which has not previously been used in this context. We introduce a novel ensemble algorithm for combining outlines using two voting schemes, a likelihood ratio test and dynamic time warping (DTW). Our goal is to minimize the human intervention required, hence we investigate alternative ways of training a classifier to determine whether an outline is in fact correct or not. We evaluate outlining and classification on a set of 1370 images. We conclude that ensembling with DTW improves performance of all outlining algorithms, that the contouring algorithm used with the DTW ensemble performs the best of those assessed, and that the most effective classifier of hand outlines assessed is a random forest applied to outlines transformed into principal components

Relational Decision‐Making in the Context of Life‐Limiting Fetal Anomalies: Two Cases of Anencephaly Diagnosis

Life‐limiting fetal diagnoses such as anencephaly require families to make decisions in which no options offered will lead to the desired outcome of a healthy newborn. Although informed choice and shared decision‐making are important aspects of ethics regarding care choices, they have limitations. In this article, 2 cases of anencephaly diagnosis are presented, and a relational decision‐making model of care is proposed as an alternative for aiding pregnant people and their families in making challenging choices in the context of perinatal care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163826/1/jmwh13161.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163826/2/jmwh13161_am.pd

Sensory Activation of Command Cells for Locomotion and Modulatory Mechanisms: Lessons from Lampreys

Sensorimotor transformation is one of the most fundamental and ubiquitous functions of the central nervous system. Although the general organization of the locomotor neural circuitry is relatively well understood, less is known about its activation by sensory inputs and its modulation. Utilizing the lamprey model, a detailed understanding of sensorimotor integration in vertebrates is emerging. In this article, we explore how the vertebrate central nervous system integrates sensory signals to generate motor behavior by examining the pathways and neural mechanisms involved in the transformation of cutaneous and olfactory inputs into motor output in the lamprey. We then review how 5-HT acts on these systems by modulating both sensory inputs and motor output. A comprehensive review of this fundamental topic should provide a useful framework in the fields of motor control, sensorimotor integration and neuromodulation