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We employ both manual and automated content analysis to update an existing dictionary (Boritz, Hayes, and Lim 2013) used to classify types of information technology weakness (ITW). Through analysis of auditors' reports on internal control filed under Section 404 of the Sarbanes-Oxley Act from 2011 through 2020, we provide a robust tool for textual analytics. Additionally, we apply OpenAI's large-language model neural networks for classification as a comparison point. We expand identification of ITW categories such as Design, Security, and Outsourcing and identify Governance as a critical new category in auditor reporting. We further expand the dictionary, capturing categories of IT risk found within current IT control frameworks (e.g., COBIT and AICPA TSCs), which we compare with content of auditor reporting. Evidence suggests stakeholders are subject to significant information asymmetry in assessing and reporting IT risk. We provide direction for future IT governance and improve application of advanced textual analysis. [ABSTRACT FROM AUTHOR]

In this audio essay, the author/speaker contemplates the perceived relationship between the voice and the speaker—the person in the voice—and asks the following questions: What does it mean when we judge that the person does not sound like they should? In terms of pedagogy and beyond, what does it mean when we judge a person as not speaking the way we think they should? How does our judgment affect and effect the speaker? [ABSTRACT FROM AUTHOR]

Research shows that racial discrimination results in adverse behavioral health outcomes for African-American young adults, including risk for depression, anxiety, and substance use. Although high levels of mindfulness have been shown to reduce risk for such health outcomes, it is unknown whether mindfulness can reduce risk as a consequence of racial discrimination, particularly among African Americans. Three-hundred and eighty-eight African-American young adults between the ages of 18 and 24 (M = 20.6, 62% female) completed measures assessing past-year experiences of racial discrimination, depressive symptoms, anxiety symptoms, alcohol use, and trait mindfulness. A positive correlation was found between racial discrimination and the behavioral health outcomes, as well as a negative correlation between mindfulness and the behavioral health outcomes. Moreover, mindfulness was found to significantly moderate the effect of racial discrimination on mood symptoms. Although mindfulness was found to lessen the effect of racial discrimination on alcohol use, this difference was not statistically significant. In line with previous literature, racial discrimination was shown to have a negative impact on behavioral health outcomes among African Americans. Moreover, our findings provide support for the buffering effect of mindfulness on mood symptoms as a consequence discrimination. This suggests that increasing mindfulness may be an effective strategy to include in interventions targeting improvement in mood symptoms for African-American young adults. However, alternative strategies may be more appropriate to address outcomes, such as alcohol use, as a consequence of racial discrimination. [ABSTRACT FROM AUTHOR]

Background and Objectives: Substance use behaviors have been identified as a risk factor that places juveniles at greater risk for engaging in delinquent behaviors and continual contact with the juvenile justice system. Currently, there is lack of research that explores comorbid factors associated with substance use, such as post-traumatic stress disorder (PTSD) symptoms, that could help identify youth who are at greatest risk. The aim of the present study was to examine if PTSD symptomology moderated the relationship between substance use disorder (SUD) symptoms and externalizing behaviors and commission of a violent crime; hypothesizing that risk would be heightened among youth with elevated SUD and PTSD symptomology compared to those with elevated SUD symptoms but lower PTSD symptoms.Method: The study included 194 predominantly male (78.4%), non-White (74.2%) juvenile justice youth between the ages of 9-18 (M = 15.36). Youth provided responses to assess PTSD symptoms, SUD symptoms, and externalizing behaviors. Commission of a violent crime was based on parole officer report.Results: Findings indicated that SUD symptomology was associated with greater externalizing behaviors at high levels of PTSD symptomology. At low levels of PTSD symptomology, SUD symptoms were inversely associated with externalizing behaviors. An interactive relationship was not observed for commission of violent crimes.Conclusions: Findings suggest that the association between SUD symptoms and externalizing behaviors among juvenile offenders may be best explained by the presence of PTSD symptomology.Scientific Significance: Addressing PTSD rather than SUD symptoms may be a better target for reducing risk for externalizing behaviors among this population of youth (Am J Addict 2019;28:29-35). [ABSTRACT FROM AUTHOR]

The folding and insertion of integral ß-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of selective and potent modulators to dissect ß-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize amonoclonal antibody that selectively inhibits an essential component of the Escherichia coli ß-barrel assembly machine, BamA. In the absence of complement or other immune factors, the unmodified antibody MAB1 demonstrates bactericidal activity against an E. coli strain with truncated LPS. Direct binding of MAB1 to an extracellular BamA epitope inhibits its ß-barrel folding activity, induces periplasmic stress, disrupts outer membrane integrity, and kills bacteria. Notably, resistance to MAB1-mediated killing reveals a link between outermembrane fluidity and protein folding by BamA in vivo, underscoring the utility of this antibody for studying ß-barrel membrane protein folding within a living cell. Identification of this BamA antagonist highlights the potential for new mechanisms of antibiotics to inhibit Gramnegative bacterial growth by targeting extracellular epitopes. [ABSTRACT FROM AUTHOR]

Multiple small-molecule inhibitors of the ß-secretase enzyme (BACE1) are under preclinical or clinical investigation for Alzheimer's disease (AD). Prior work has illustrated robust lowering of central amyloid β (A#946;) after acute administration of BACE1 inhibitors. However, very few studies have assessed the overall impact of chronically administered BACE1 inhibitors on brain amyloid burden, neuropathology, and behavioral function in aged preclinical models. We investigated the effects of a potent nonbrain-penetrant BACE1 inhibitor, delivered directly to the brain using intracerebroventricular infusion in an aged transgenic mouse model. Intracerebroventricular infusion of the BACE1 inhibitor (0.3-23.5 μ/d) for 8 weeks, initiated in 17-month-old Tg2576 mice, produced dose-dependent increases in brain inhibitor concentrations (0.2-13 μM). BACE1 inhibition significantly reversed the behavioral deficit in contextual fear conditioning, and reduced brain Aß levels, plaque burden, and associated pathology (e.g., dystrophic neurites), with maximal effects attained with ~ 1 μg/d dose. Strikingly, the BACE1 inhibitor also reversed amyloid pathology below baseline levels (amyloid burden at the start of treatment), without adversely affecting cerebral amyloid angiopathy, microhemorrhages, myelination, or neuromuscular function. Inhibitor-mediated decline in brain amyloid pathology was associated with an increase in microglial ramification. This is the first demonstration of chronically administered BACE1 inhibitor to activate microglia, reverse brain amyloid pathology, and elicit functional improvement in an aged transgenic mouse model. Thus, engagement of novel glial-mediated clearance mechanisms may drive diseasemodifying therapeutic benefit with BACE1 inhibition in AD. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2–1% of all births, and causes birth defects and developmental abnormalities, including sensorineural hearing loss and developmental delay. Several key studies have established the guinea pig as a tractable model for the study of congenital HCMV infection and have shown that polyclonal antibodies can be protective [1]–[3]. In this study, we demonstrate that an anti-guinea pig CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody protects against fetal infection and loss in the guinea pig. Furthermore, we have delineated the kinetics of GPCMV congenital infection, from maternal infection (salivary glands, seroconversion, placenta) to fetal infection (fetus and amniotic fluid). Our studies support the hypothesis that a neutralizing monoclonal antibody targeting an envelope GPCMV glycoprotein can protect the fetus from infection and may shed light on the therapeutic intervention of HCMV congenital infection in humans. [ABSTRACT FROM AUTHOR]

Huntington's disease is caused by expression of a mutant form of Huntingtin protein containing an expanded polyglutamine repeat. One possible treatment for Huntington's disease may be to reduce expression of mutant Huntingtin in the brain via RNA interference. Unless the therapeutic molecule is designed to be allele-specific, both wild-type and mutant protein will be suppressed by an RNA interference treatment. A key question is whether suppression of wild-type as well as mutant Huntingtin in targeted brain regions can be tolerated and result in a net benefit to patients with Huntington's disease. Whether Huntingtin performs essential functions in the adult brain is unclear. Here, we tested the hypothesis that the adult primate brain can tolerate moderately reduced levels of wild-type Huntingtin protein for an extended period of time. A serotype 2 adeno-associated viral vector encoding for a short hairpin RNA targeting rhesus huntingtin messenger RNA (active vector) was bilaterally injected into the striatum of four adult rhesus monkeys. Four additional animals received a comparable vector encoding a scrambled control short hairpin RNA (control vector). General health and motor behaviour were monitored for 6 months. Upon termination, brain tissues were sampled and assessed blindly for (i) huntingtin messenger RNA knockdown; (ii) Huntingtin protein expression; and (iii) neuropathological changes. Reduction in wild-type huntingtin messenger RNA levels averaging ∼30% was measured in the striatum of active vector recipients 6 months post-injection. A widespread reduction in Huntingtin protein levels was also observed by immunohistochemistry in these animals, with an average protein reduction of ∼45% relative to controls measured by western blot analysis in the putamen of active vector recipients. As with control vector recipients, no adverse effects were observed behaviourally, and no neurodegeneration was found on histological examination of active vector recipients. Our results suggest that long-term partial suppression of wild-type Huntingtin may be safe, and thus if a comparable level of suppression of mutant Huntingtin is beneficial, then partial suppression of both wild-type and mutant Huntingtin may result in a net benefit in patients with heterozygous Huntington's disease. [ABSTRACT FROM AUTHOR]

Although immunization against amyloid-β (Aβ) holds promise as a disease-modifying therapy for Alzheimer disease (AD), it is associated with an undesirable accumulation of amyloid in the cerebrovasculature [i.e., cerebral amyloid angiopathy (CAA)] and a heightened risk of micro-hemorrhages. The central and peripheral mechanisms postulated to modulate amyloid with anti-Aβ immunotherapy remain largely elusive. Here, we compared the effects of prolonged intracerebroventricular (icv) versus systemic delivery of anti-Aβ antibodies on the behavioral and pathological changes in an aged Tg2576 mouse model of AD. Prolonged icy infusions of anti-Aβ antibodies dose-dependently reduced the parenchymal plaque burden, astrogliosis, and dystrophic neurites at doses 10to 50-fold lower than used with systemic delivery of the same antibody. Both icy and systemic anti-Aβ antibodies reversed the behavioral impairment in contextual fear conditioning. More importantly, unlike systemically delivered anti-Aβ antibodies that aggravated vascular pathology, icv-infused antibodies globally reduced CAA and associated micro-hemorrhages. We present data suggesting that the divergent effects of icv-delivered anti-Aβ antibodies result from gradually engaging the local (i.e., central) mechanisms for amyloid clearance, distinct from the mechanisms engaged by high doses of anti-Aβ antibodies that circulate in the vasculature following systemic delivery. With robust efficacy in reversing AD-related pathology and an unexpected benefit in reducing CAA and associated micro-hemorrhages, icv-targeted passive immunotherapy offers a promising therapeutic approach for the long-term management of AD. [ABSTRACT FROM AUTHOR]

We previously reported that a (CTG)n expansion causes spinocerebellar ataxia type 8 (SCA8), a slowly progressive ataxia with reduced penetrance. We now report a transgenic mouse model in which the full-length human SCA8 mutation is transcribed using its endogenous promoter. (CTG)116 expansion, but not (CTG)11 control lines, develop a progressive neurological phenotype with in vivo imaging showing reduced cerebellar-cortical inhibition. 1C2-positive intranuclear inclusions in cerebellar Purkinje and brainstem neurons in SCA8 expansion mice and human SCA8 autopsy tissue result from translation of a polyglutamine protein, encoded on a previously unidentified antiparallel transcript (ataxin 8, ATXN8 ) spanning the repeat in the CAG direction. The neurological phenotype in SCA8 BAC expansion but not BAC control lines demonstrates the pathogenicity of the (CTG-CAG)n expansion. Moreover, the expression of noncoding (CUG)n expansion transcripts (ataxin 8 opposite strand, ATXN8OS ) and the discovery of intranuclear polyglutamine inclusions suggests SCA8 pathogenesis involves toxic gain-of-function mechanisms at both the protein and RNA levels. [ABSTRACT FROM AUTHOR]

The purpose of this article is to describe the steps to the development of a successful Physical Education Teacher Education (PETE) workshop. PETE professors share a common goal for improving undergraduate pedagogy instruction. Pedagogy issues and concerns include curriculum decisions, field experience assignments, technology in the classroom, peer teaching ideas, assessment, electronic portfolios and textbook decisions. As a way of sharing ideas and brainstorming, university and college PETE professors in Tennessee meet annually at rotating campus sites. A core group of organizers plan the workshop based on interests and concerns express by attendees. The ultimate goal of the workshops is to better prepare future physical educators who are currently enrolled in university and college undergraduate licensure programs. The Tennessee Association for Health, Physical Education, Recreation and Dance (TAHPERD) sponsors the annual event. [ABSTRACT FROM AUTHOR]

We have discovered that β-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families. Two families have separate in-frame deletions of 39 and 15 bp, and a third family has a mutation in the actin/ARP1 binding region. β-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane. We found marked differences in EAAT4 and GluRδ2 by protein blot and cell fractionation in SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not mutant β-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling. [ABSTRACT FROM AUTHOR]

We evaluated relationships between climatological variables and abundance of larval yellow perch (Perca flavescens) in eastern South Dakota glacial lakes. Age-0 yellow perch were collected using a 0.75 m diameter ichthyoplankton net from May through mid-June at 7 to 10 d intervals. Highest correlation coefficients with larval yellow perch abundance were for April total precipitation (r=0.95-0.99; P=0.09- 0.01; three lakes), mean March wind speed (r=-0.98 to -0.99; P=0.02-0.006; two lakes), mean of May average daily temperatures (r=0.78; P=0.12; one lake) and mean May wind speed (r=-0.82; P=0.02; one lake). Given the low number of years in some samples, individual years at times had undue influence on the relationship, resulting in high correlation coefficients. Multiple regression modeling resulted in improved models for only two of the seven lakes (R²=0.90-0.98; P=0.05-0.02). However, March through May weather patterns in some combination were related to larval yellow perch abundance in all seven study lakes. Larval abundance tended to be higher in years with less wind, more precipitation, and warmer air temperatures. Whether wind, temperature, or precipitation were most influential seemed to vary by lake. [ABSTRACT FROM AUTHOR]

Examines the near-saturated mutagenesis and functional analysis of nucleotides in the gag region of Moloney murine leukemia virus using genetic footprinting. Cell transfection and infection; Creation of a library of insertional mutations in gag; Viral replication as selection for gag function.

Presents a study that analyzed the relationships between alewives population characteristics and physiochemical lake variables in lakes in Connecticut. Assessment of the characteristics of alewife populations; Analysis of the growth rates of alewives; Correlation between alewife growth rate and lake depth.

The article presents a collection of essays to expand the understanding of lesbians at midlife by exploring complexities of relationships and bonds that sustain and nurture the lives. It spotlights relationships with friends, lovers, parents and children and experiences with dating, recovery and loss. For most lesbian and heterosexual women, midlife is a positive, spirited time. But midlife is also a time of change and growth uniquely informed by self-perceptions accumulated over half a lifetime of experiences and energized by the awareness of the finiteness of lives. Consolidation and expansion is the internal process of midlife development, and the external process is the reshaping of lives to reflect and affirm a new midlife sense. Thus, a common narrative among women at midlife which reflects this process is the acquisition of greater self-awareness and increased self-acceptance. Midlife tales typically involve transition and change, when a woman comes to terms with who she is through self-acceptance or through retrieving a self previously limited by family loyalties.

A method (habituation test) for studying habituation of the palmar skin conductance response (SCR) during iterative photostimulation in mice is described. Twenty drugs known for their CNS stimulant activity and/or beneficial action on learning were tested for their antagonism toward habituation. With most of the drugs tested, the delay in SCR extinction was dose-dependent. From the corresponding regression equations, the standard delaying doses were computed and used for classification. Fenozolone was the most active product. In descending order follow dexamphetamine and piracetam, then other amphetamines. Locomotor activity tests were run in parallel with habituation tests and the two sets of results compared. Reliability of habituation test was checked. The responsiveness of the test and the significance of the results are discussed. The applicability of the habituation test in psychopharmacological research is argued by its sensitivity to piracetam, whose nootropic activity is not detectable by classic behavioral methods. The habituation test makes it possible to test drugs for their effects on the maintenance of attention during monotonous stimulation and, more generally, for their psychic enhancement activity whatever the mechanism involved. It is thus likely to be a suitable test for nooanaleptics (in the broad meaning of the term). [ABSTRACT FROM AUTHOR]

An apparatus and a quantitative method for studying the spontaneous palmar conductivity (SPC) and the psychogalvanic reaction (PGR) in mice are described. Several psycholeptics (neuroleptics, tranquillizers, hypnotics) were tested. In order to assess the specificity of the method, several other pharmacological agents (muscle relaxants, neuromusclar blocking agents, anticholinergics, α-adrenolytics) were tested. A comparison of the active doses of these various products on SPC, PGR, prehension and traction reflexes shows that psycholeptics and more particularly neuroleptics and tranquillizers inhibit PGR at low dosages. These are smaller than the motor test inhibitory dosages and far lower than LD50. Providing one discounts drugs inhibiting the PGR by peripheral anticholinergic or adrenolytic activity and those which inhibit the PGR at dosages which are similar to the motor depressant dosages, the method is valid for screening and studying psycholeptic drugs. [ABSTRACT FROM AUTHOR]

When the thermophilic mold Thermoascus aurantiacus var. levisporus was grown in a modified Czapek Dox medium containing casein the filtrate was found to contain proteolytic activity. The maximum production of activity occurred at 50 ° C in a medium containing 8% casein. The filtrate was subjected to ammonium sulfate fractionation and chromatography on DEAE-cellulose. Two proteases were separated. No further work was done on protease II. Protease I was further purified by gel filtration on Sephadex G 100-200. It showed a 40-fold purification with a final recovery of approximately 25%. It is a neutral protease with a pH optimum at 7.0. The optimal activity of the enzyme occurred in 0.02 M phosphate buffer but was completely inhibited at a concentration of 0.1 M. The optimum temperature for casein hydrolysis was found to be 55 ° C. The enzyme was inhibited by Hg but was greatly stimulated by Cu and mercaptoethanol. Metallo and sulfhydryl agents had no significant effect on enzyme activity. [ABSTRACT FROM AUTHOR]

Presents information on the findings of a survey conducted on the history of psychology courses. Dependence of faculty on textbooks to organize their courses; Common characteristics of course syllabi; Characteristics of ancient and modern courses.

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In mice, iterative photostimulation results in habituation, detected in the palmar skin conductance response. Psychoanaleptics delay this habituation in proportion to the dose administered. [ABSTRACT FROM AUTHOR]

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)