Poly(ADP)-Ribose Polymerase Activity in the Eukaryotic Mono-ADP-Ribosyl Transferase, ART2: a Dissertation

The glycophosphatidylinositol(GPI)-linked membrane protein ART2 is an antigenic determinant for T lymphocytes that regulate the expression of diabetes in the BB/W rat model. Though little is understood of the physiologic role of ART2 on T lymphocytes, ART2 is a member of the mono-ADP-ribosyl transferase subgroup ofthe ADP-ribosyl transferase (ART) protein family. The ART protein family, which traditionally has been divided into mono-ADP-ribosyl transferases (mono-ARTs), poly(ADP)-ribose polymerases (PARPs), and ADP-ribosyl cyclases, influences various aspects of cellular physiology including: apoptosis, DNA damage repair, chromatin remodeling, telomere replication, cellular transport, immune regulation, neuronal function, and bacterial virulence. A structural alignment of ART2.2 with chicken PARP indicated the potential for ART2.2 to catalyze ADP-ribose polymers in an activity thought to be specific to the PARP subgroup and important for their regulation of nuclear processes. Kinetic studies determined that the auto-ADP-ribosyl transferase activity of ART2.2 is multitmeric and heterogeneous in nature. Hydroxylamine-cleaved ADP-ribose moieties from the ART2.2 multimers ran as polymers on a modified sequencing gel, and digestion of the polymers with snake-venom phosphodiesterase produced AMP and the poly(ADP)ribose-specific product, PR-AMP, which was resolved by analytical HPLC and structurally confirmed by ESI-MS. The ratio of AMP to PR-AMP was higher than that of PARP raising the possibility that the ART2.2 polymers had a different branching structure than those of PARP. This alternative branching was confirmed by the presence of ribose phosphate polymers in the snake venom phophodiesterase treated samples. The site of the auto-poly(ADP)-ribose modification was determined to be R185, a residue previously proposed to influence the level of auto-ADP ribosylation of ART2.2 by mutational analysis. These data provide the first demonstration of a hybrid between mono-ARTs and PARPs and are the earliest indication that PARP-like enzymes can exist outside the nucleus and on the cell surface

Generative Learning Strategy Use and Self-Regulatory Prompting in Digital Text

The digital revolution is shifting print-based textbooks to digital text, and it has afforded the opportunity to incorporate meaningful learning strategies and otherwise separate metacognitive activities directly into these texts as embedded support. A sample of 89 undergraduates read a digital, expository text on the basics of photography. The treatment prompted the reader with selfregulatory questions and embedded a generative strategy, paraphrasing, and confirmed previous research on the relationships between prior knowledge and level of self-regulation on reading comprehension. A one-way between subjects ANOVA revealed significance for the level of self-regulation on comprehension-level items and for the level of prior knowledge on recall-level items. ANOVA also indicated that the quality of paraphrasing has a significant impact on recall-level and overall performance on the posttest. Further, participants were generally positive towards the instructional materials, which suggests willingness, and in some cases, preference, to reading in a digital format while experiencing embedded, metacognitive instructional interventions. It is recommended that comprehension may be enhanced by providing deeper training on the use of the generative strategy and by increasing motivation prior to interacting with the text in order to capitalize on the unique advantages of digital materials

On the integration of object-oriented and process-oriented computation in persistent environments

Persistent programming is concerned with the construction of large and long lived systems of data [1,2]. Such systems have traditionally required concurrent access for two reasons. The first is that of speed, be it access speed for multiple users or execution speed for parallel activities. The second reason for concurrency is to control the complexity of large systems by decomposing them into parallel activities. This process-oriented approach to system construction has much in common with the object-oriented approach. We will demonstrate, in this paper, the facilities of the language Napier [17] which allows the integration of the two methodologies along with a persistent environment to provide concurrently accessed object-oriented databases.Othe

Disodium (2RS,3SR)-tartrate

The asymmetric unit of the anhydrous title compound, 2Na+·C4H4O6 2−, contains two sodium cations and one tartrate anion. Each sodium ion is six coordinate, with bonding to six O atoms from both the carboxyl­ate and hydroxyl groups of the anion. A three-dimensional coordination network is formed with sodium ions stacking in layers along the c-axis direction. This network is supported by additional O—H⋯O hydrogen bonds

Supreme Court Brief Amicus Curiae of Administrative Law Scholars in Support of Neither Party

This brief on behalf of 29 administrative law scholars takes no position on whether Administrative Law Judges (ALJs) are employees or inferior officers. It urges the Court to issue an opinion that respects the decision that Congress made unanimously in 1946 to enact numerous statutory safeguards that assure that ALJs have decisional independence from the agencies where they work while assuring that agencies retain control over the policy content and legal basis for any decision made in an adjudication in which an ALJ presides. The brief describes the fifteen years of study and deliberation that led to the unanimous decision of Congress to enact the Administrative Procedure Act (APA) in 1946. It describes the particular attention that Congress devoted to the critical task of providing ALJs with the combination of statutory safeguards that minimize the risk that they will favor the agencies for whom they adjudicate cases while assuring that the agencies retain control of the policy content of any decision made in such an adjudication. It then describes the series of opinions the Supreme Court issued during the 1950s in which the Justices unanimously praised the provisions of the APA that assure that ALJs conduct adjudicatory hearings in an unbiased manner, explained the importance of those statutory provisions in protecting the values reflected in the Due Process Clause, and urged Congress to make those safeguards applicable to all agency adjudications. It concludes by urging the Court to issue an opinion that respects the decision that Congress made in 1946 to insulate ALJs from potential sources of pro-agency bias by including in the APA a combination of provisions that confer decisional independence on ALJs

(R,R)-Disynephrine ether bis­(hydrogen sulfate)

The asymmetric unit of the title compound [systematic name: (R,R)-2,4-bis­(4-hydroxy­phen­yl)-N,N′-dimethyl-3-oxapentane-1,5-diammonium bis­(hydrogen sulfate)], C18H26N2O3 2+·2HSO4 −, contains one half-cation and one hydrogen sulfate anion. The cation has crystallographically imposed twofold symmetry with the rotation axis passing through the central ether O atom. Hydrogen bonds between the hydr­oxy group and amine H atoms of the cation to two hydrogen sulfate anions link the three ions in a ring motif. A three-dimensional network is accomplished by additional O—H⋯O hydrogen bonds between the anions and by N—H⋯O hydrogen bonds between the cations. Disorder with equally occupied sites affects the H-atom position in the anion

Strengthening impact assessment: a call for integration and focus

We suggest that the impact assessment community has lost its way based on our observation that impact assessment is under attack because of a perceived lack of efficiency. Specifically, we contend that the proliferation of different impact assessment types creates separate silos of expertise and feeds arguments for not only a lack of efficiency but also a lack of effectiveness of the process through excessive specialisation and a lack of interdisciplinary practice. We propose that the solution is a return to the basics of impact assessment with a call for increased integration around the goal of sustainable development and focus through better scoping. We rehearse and rebut counter arguments covering silo-based expertise, advocacy, democracy, sustainability understanding and communication. We call on the impact assessment community to rise to the challenge of increasing integration and focus, and to engage in the debate about the means of strengthening impact assessment

Condensation properties of stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1

RNA regulation in mammalian cells requires complex physical compartmentalisation, using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic dystrophy type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from an expansion of nucleotides CTG (CTGexp) in the DNA encoding DM1 protein kinase (DMPK). The cellular hallmark of DM1 is the formation of nuclear foci that contain expanded DMPK RNA (CUGexp) (with thymine instead of uracil). We report here the deregulation of stress granules (SGs) and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of SGs suggest an altered ability of cells to respond to stress associated with DM1, while changes to the structure and dynamics of SGs and P-bodies suggest that a widespread alteration to the biophysical properties of cellular structures is a consequence of the presence of CUGexp RNA.</p

Home‐Based Cardiac Rehabilitation Alone and Hybrid With Center‐Based Cardiac Rehabilitation in Heart Failure: A Systematic Review and Meta‐Analysis

Background Center‐based cardiac rehabilitation (CBCR) has been shown to improve outcomes in patients with heart failure (HF). Home‐based cardiac rehabilitation (HBCR) can be an alternative to increase access for patients who cannot participate in CBCR. Hybrid cardiac rehabilitation (CR) combines short‐term CBCR with HBCR, potentially allowing both flexibility and rigor. However, recent data comparing these initiatives have not been synthesized. Methods and Results We performed a meta‐analysis to compare functional capacity and health‐related quality of life (hr‐QOL) outcomes in HF for (1) HBCR and usual care, (2) hybrid CR and usual care, and (3) HBCR and CBCR. A systematic search in 5 standard databases for randomized controlled trials was performed through January 31, 2019. Summary estimates were pooled using fixed‐ or random‐effects (when I2\u3e50%) meta‐analyses. Standardized mean differences (95% CI) were used for distinct hr‐QOL tools. We identified 31 randomized controlled trials with a total of 1791 HF participants. Among 18 studies that compared HBCR and usual care, participants in HBCR had improvement of peak oxygen uptake (2.39 mL/kg per minute; 95% CI, 0.28–4.49) and hr‐QOL (16 studies; standardized mean difference: 0.38; 95% CI, 0.19–0.57). Nine RCTs that compared hybrid CR with usual care showed that hybrid CR had greater improvements in peak oxygen uptake (9.72 mL/kg per minute; 95% CI, 5.12–14.33) but not in hr‐QOL (2 studies; standardized mean difference: 0.67; 95% CI, −0.20 to 1.54). Five studies comparing HBCR with CBCR showed similar improvements in functional capacity (0.0 mL/kg per minute; 95% CI, −1.93 to 1.92) and hr‐QOL (4 studies; standardized mean difference: 0.11; 95% CI, −0.12 to 0.34). Conclusions HBCR and hybrid CR significantly improved functional capacity, but only HBCR improved hr‐QOL over usual care. However, both are potential alternatives for patients who are not suitable for CBCR

Millennials, Equity, and the Rule of Law: 2014 National Lawyers Convention, \u3ci\u3eHow First Amendment Procedures Protect First Amendment Substance\u3c/i\u3e

A panel, at the National Lawyers Convention, discussed procedure as it relates to First Amendment rights. The panel set forth how First Amendment procedures have historically protected First Amendment substance and discussed modern applications of the issue. For example, the prior restraint doctrine, overbreadth doctrine, the allocation of the burden of proof and relaxation of ripeness rules have important implications for challenging restrictions on speech and defending against libel and defamation. The interaction of free speech and due process is often seen in litigation involving civil harassment orders, or civil protection orders. In many jurisidictions the definition of harassment permits the finding that harassment can be based solely on speech, meaning speech itself can provide a basis for liabilty. In addition, speech may be restricted as a remedy in litigation addressing harassment. Investigations of wrongdoing in the realm of campaign finance law and political speech cases can also have serious implications for speech, both reputational and legal. Further cases involving political speech and campaign finance once exclusively litigated in the civil arena, are now the subject of criminal investigations and prosecutions. This is particularly problematic where many issues in this area remain unsettled. Good lawyering is particularly important in First Amendment cases. Ineffective assistance of counsel can be considered as great an evil in First Amendment cases as in criminal cases. Unfortunately, practicing lawyers often do not understand the process by which constitutional facts are pleaded and proved in First Amendment cases and this problem begins with the way Constitutional Law 101 is taught in law schools. In proving facts in First Amendment litigation the question becomes how does the government prove its justification of a restriction on speech or how does one opposing the government’s restriction on speech respond when the government asserts certain interests as being their justification. In First Amendment litigation the government often relies on legislative facts – newspaper reports, television stories, and criminal cases discussed in the media, arguably the government should be obligated to present more than rumors and speculation