Morphological variation of the foraminifer Ammonia beccarii (Linné) from the Atlantic coast of the United States

24 p., 4 fig.http://paleo.ku.edu/contributions.htm

Ground Motion Amplification from Vertical Propagation of Earthquake Waves

The paper is directed to follow a procedure where seismic responses are identified and recommendations to proceed with their applications are made quickly and economically, before engaging in a complex analysis. It is not intended for selecting design soil parameters or earthquake parameters for the final design of any specific dam. A selected earthquake accelerogram will produce response accelerations and strains that will cover a significant variety of accelerograms in terms of severity of earthquake damage to an earth dam. Scaling-up and scaling-down the selected outcrop motion broadens the spectrum of seismic response analyses using simple and effective SHAKE program for making decision on the need for further more sophisticated analyses, particularly when the 1-D response analysis shows potential problems. It is inappropriate to base the judgment of final seismic response of dam on 1-D analysis,. The traditional dynamic modulus reduction curves have been shown to be appropriate up to one percent strain. The analysis performed in this paper shows the maximum strain to be smaller than 0.5%. The Mexico City (MC) clay is used to demonstrate different soil types do exist in nature and, in some situation, can show quite different responses in different intensity seismic events. First, hypothetical soil deposits are used in evaluating factors affecting PHA variation in a soil deposit, and then, the findings are referenced in the seismic response of an embankment dam in the west coast of the United States. The shear wave velocities of this embankment dam were carefully selected, using educated judgment, to represent a compacted embankment

Antibacterial mechanisms identified through structural systems pharmacology

Background: The growing discipline of structural systems pharmacology is applied prospectively in this study to predict pharmacological outcomes of antibacterial compounds in Escherichia coli K12. This work builds upon previously established methods for structural prediction of ligand binding pockets on protein molecules and utilizes and expands upon the previously developed genome scale model of metabolism integrated with protein structures (GEM-PRO) for E. coli, structurally accounting for protein complexes. Carefully selected case studies are demonstrated to display the potential for this structural systems pharmacology framework in discovery and development of antibacterial compounds. Results: The prediction framework for antibacterial activity of compounds was validated for a control set of well-studied compounds, recapitulating experimentally-determined protein binding interactions and deleterious growth phenotypes resulting from these interactions. The antibacterial activity of fosfomycin, sulfathiazole, and trimethoprim were accurately predicted, and as a negative control glucose was found to have no predicted antibacterial activity. Previously uncharacterized mechanisms of action were predicted for compounds with known antibacterial properties, including (1-hydroxyheptane-1,1-diyl)bis(phosphonic acid) and cholesteryl oleate. Five candidate inhibitors were predicted for a desirable target protein without any known inhibitors, tryptophan synthase β subunit (TrpB). In addition to the predictions presented, this effort also included significant expansion of the previously developed GEM-PRO to account for physiological assemblies of protein complex structures with activities included in the E. coli K12 metabolic network. Conclusions: The structural systems pharmacology framework presented in this study was shown to be effective in the prediction of molecular mechanisms of antibacterial compounds. The study provides a promising proof of principle for such an approach to antibacterial development and raises specific molecular and systemic hypotheses about antibacterials that are amenable to experimental testing. This framework, and perhaps also the specific predictions of antibacterials, is extensible to developing antibacterial treatments for pathogenic E. coli and other bacterial pathogens

PaleoBank, A Relational Database for Invertebrate Paleontology: The Data Model

7 p., 1 fig., 2 tables.http://paleo.ku.edu/contributions.htm

Predicting post-trauma stress symptoms from pre-trauma psychophysiologic reactivity, personality traits and measures of psychopathology

Background: Most individuals exposed to a traumatic event do not develop post-traumatic stress disorder (PTSD), although many individuals may experience sub-clinical levels of post-traumatic stress symptoms (PTSS). There are notable individual differences in the presence and severity of PTSS among individuals who report seemingly comparable traumatic events. Individual differences in PTSS following exposure to traumatic events could be influenced by pre-trauma vulnerabilities for developing PTSS/PTSD. Methods Pre-trauma psychological, psychophysiological and personality variables were prospectively assessed for their predictive relationships with post-traumatic stress symptoms (PTSS). Police and firefighter trainees were tested at the start of their professional training (i.e., pre-trauma; n = 211) and again several months after exposure to a potentially traumatic event (i.e., post-trauma, n = 99). Pre-trauma assessments included diagnostic interviews, psychological and personality measures and two psychophysiological assessment procedures. The psychophysiological assessments measured psychophysiologic reactivity to loud tones and the acquisition and extinction of a conditioned fear response. Post-trauma assessment included a measure of psychophysiologic reactivity during recollection of the traumatic event using a script-driven imagery task. Results: Logistic stepwise regression identified the combination of lower IQ, higher depression score and poorer extinction of forehead (corrugator) electromyogram responses as pre-trauma predictors of higher PTSS. The combination of lower IQ and increased skin conductance (SC) reactivity to loud tones were identified as pre-trauma predictors of higher post-trauma psychophysiologic reactivity during recollection of the traumatic event. A univariate relationship was also observed between pre-trauma heart rate (HR) reactivity to fear cues during conditioning and post-trauma psychophysiologic reactivity. Conclusion: The current study contributes to a very limited literature reporting results from truly prospective examinations of pre-trauma physiologic, psychologic, and demographic predictors of PTSS. Findings that combinations of lower estimated IQ, greater depression symptoms, a larger differential corrugator EMG response during extinction and larger SC responses to loud tones significantly predicted higher PTSS suggests that the process(es) underlying these traits contribute to the pathogenesis of subjective and physiological PTSS. Due to the low levels of PTSS severity and relatively restricted ranges of outcome scores due to the healthy nature of the participants, results may underestimate actual predictive relationships

Design, Synthesis, and Biological Activity of 5\u27-Phenyl-1,2,5,6-tetrahydro-3,3\u27-bipyridine Analogues as Potential Antagonists of Nicotinic Acetylcholine Receptors

Starting from a known non-specific agonist (1) of nicotinic acetylcholine receptors (nAChRs), rationally guided structural-based design resulted in the discovery of a small series of 5′-phenyl-1,2,5,6-tetrahydro-3,3′-bipyridines (3a – 3e) incorporating a phenyl ring off the pyridine core of 1. The compounds were synthesized via successive Suzuki couplings on a suitably functionalized pyridine starting monomer 4 to append phenyl and pyridyl substituents off the 3- and 5-positions, respectively, and then make subsequent modifications on the flanking pyridyl ring to provide target compounds. Compound 3a is a novel antagonist which is highly selective for α3β4 nAChR (Ki = 123 nM) over the α4β2, and α7 receptors

Reproductive Health Disparities: Pap Knowledge and Screening Rates among Asian Pacific Islander College Women

A Papanicolaou test is the most effective procedure for detecting cervical cancer. Unfortunately, many young Asian Pacific Islander (API) college women are unaware of this procedure and do not take precaution against cervical cancer. This paper reports disaggregated data on Pap knowledge and screening rates of female students at a four-year university and suggests recommendations to healthcare providers to improve Pap screening rates. Using a communitybased participatory research (CBPR) approach, a cross-sectional study was administered using a web-based anonymous survey (N=618). The survey results indicated that participants who were least likely to know about Pap tests were 18-21 years old, API, uninsured, and not in a committed relationship. Slightly more than half (52%) of API females received a screening compared to 82.4% of white females. The most influential people for Pap screening were doctors (43%) and the least influential people were mothers (18.8%) and friends (7.8%). This study expands the literature on Pap knowledge and screenings among API college students and provides culturally appropriate recommendations to improve screening rates

Hemodynamic Effects of Epinephrine, Bicarbonate and Calcium in the Early Postnatal Period in a Lamb Model of Single-Ventricle Physiology Created In Utero

ObjectivesA reproducible fetal animal model of single-ventricle physiology was created to examine the effects of pharmacologic agents commonly used in the perinatal and perioperative intensive care management of patients with a single ventricle.BackgroundSingle-ventricle physiology is characterized by parallel pulmonary and systemic circulations, with effective blood flow to each determined by the relative resistances in the pulmonary and systemic vascular beds. Perinatal and perioperative management of these patients is largely based on empiric observations and differs considerably between institutions and is further complicated by the transitional physiology of the newborn. The lack of animal models of single-ventricle physiology has hindered the understanding of this problem.MethodsA 10-mm, Damus-Kaye-Stansel-type aortopulmonary anastomosis was created in 10 fetal sheep at 140±1.2 days of gestation. The main pulmonary artery was ligated distally, and pulmonary blood flow (Qp) was provided through a 5-mm aortopulmonary shunt. Eight lambs were delivered at term and placed on cardiopulmonary bypass (30 min) 48 to 72h after birth. Pharmacologic interventions (0.1Mg/kg body weight per min of epinephrine, 2mEq/kg of sodium bicarbonate and 10mg/kg of calcium chloride) were performed before and after bypass, and hemodynamic responses were observed. The response to the epinephrine bolus was determined only in the postbypass study.ResultsBoth before and after bypass, epinephrine infusion and calcium and bicarbonate administration increased Qp and systemic blood flow (Qs) (total cardiac output) but produced only small changes in the Qp/Qs ratio (-0.5% to -7.3% change). With the epinephrine bolus, Qp increased enormously, and the Qp/Qs ratio increased by 584% (p < 0.001).ConclusionsIn neonatal lambs with single-ventricle physiology created in utero, epinephrine infusion and calcium and bicarbonate administration increased total cardiac output without significantly compromising the Qp/Qs ratio. However, epinephrine bolus seems to be hemodynamically detrimental in circumstances of single-ventricle physiology and should be used with caution and probably in relatively lower doses in the resuscitation of patients with single-ventricle physiology. Further investigation of the dose-dependent effects and the effects of prolonged administration of common pharmacologic agents will enable better management of patients with single-ventricle physiology

iPSC Modeling of Presenilin1 Mutation in Alzheimer's Disease with Cerebellar Ataxia.

Disease modeling of Alzheimer's disease (AD) has been hampered by the lack of suitable cellular models while animal models are mainly based on the overexpression of AD-related genes which often results in an overemphasis of certain pathways and is also confounded by aging. In this study, we therefore developed and used induced pluripotent stem cell (iPSC) lines from a middle-aged AD patient with a known presenilin 1 (PSEN1) mutation (Glu120Lys; PS1-E120K) and as a control, an elderly normal subject. Using this approach, we demonstrated that the extracellular accumulation of Aβ was dramatically increased in PS1-E120K iPSC-derived neurons compared with the control iPSC line. PS1-E120K iPSC-derived neurons also exhibited high levels of phosphorylated tau, as well as mitochondrial abnormalities and defective autophagy. Given that the effect of aging is lost with iPSC generation, these abnormal cellular features are therefore indicative of PSEN1-associated AD pathogenesis rather than primary changes associated with aging. Taken together, this iPSC-based approach of AD modeling can now be used to better understand AD pathogenesis as well as a tool for drug discovery.This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2746) and a grant (2016-0588) from the Asan Institute for Life Sciences

Handwriting speed in children with Developmental Coordination Disorder: Are they really slower?

This is the post-print version of the final paper published in Research in Developmental Disabilities. The published article is available at the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 Elsevier B.V.Handwriting difficulties are often included in descriptions of Developmental Coordination Disorder (DCD). They are cited as the most common reason for referral to health professionals following parent and teacher concerns about slow and untidy writing. The aim of this study was to compare handwriting performance in English children with and without DCD across a range of writing tasks, to gain a better understanding of the nature of ‘slowness’ so commonly reported. Twenty-eight 8–14 year-old children with a diagnosis of DCD participated in the study, with 28 typically developing age and gender matched controls. Participants completed the four handwriting tasks from the Detailed Assessment of Speed of Handwriting (DASH) and wrote their own name; all on a digitising writing tablet. The number of words written, speed of pen movements and the time spent pausing during the tasks were calculated. The findings confirmed what many professionals report, that children with DCD produce less text than their peers. However, this was not due to slow movement execution, but rather a higher percentage of time spent pausing. Discussion centres on the understanding of the pausing phenomenon in children with DCD and areas for further research.Oxford Brookes Universit