29 research outputs found

    The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network

    Get PDF
    The small-molecule inhibitor Exo2 {4-hydroxy-3-methoxy-(5,6,7,8-tetrahydrol[1]benzothieno[2,3-d]pyrimidin-4-yl)hydraz-one benzaldehyde} has been reported to disrupt the Golgi apparatus completely and to stimulate Golgiā€“ER (endoplasmic reticulum) fusion in mammalian cells, akin to the well-characterized fungal toxin BFA (brefeldin A). It has also been reported that Exo2 does not affect the integrity of the TGN (trans-Golgi network), or the direct retrograde trafficking of the glycolipid-binding cholera toxin from the TGN to the ER lumen. We have examined the effects of BFA and Exo2, and found that both compounds are indistinguishable in their inhibition of anterograde transport and that both reagents significantly disrupt the morphology of the TGN in HeLa and in BS-C-1 cells. However, Exo2, unlike BFA, does not induce tubulation and merging of the TGN and endosomal compartments. Furthermore, and in contrast with its effects on cholera toxin, Exo2 significantly perturbs the delivery of Shiga toxin to the ER. Together, these results suggest that the likely target(s) of Exo2 operate at the level of the TGN, the Golgi and a subset of early endosomes, and thus Exo2 provides a more selective tool than BFA for examining membrane trafficking in mammalian cells

    A history of baseball in Asia: assimilating, rejecting and remaking America's game

    No full text
    published_or_final_versionHistoryMasterMaster of Philosoph

    The Big Chair: The Smooth Hops and Bad Bounces from the Inside World of the Acclaimed Los Angeles Dodgers General Manager

    No full text
    During his tenure with the Dodgers, Colletti had the highest winning percentage of any general manager in the National League. In The Big Chair (coauthored by Joseph A. Reaves), he lets listeners in on the real GM experience - something no one in the position has ever done before - sharing the inner workings of three of the top franchises in the sport, revealing the out-of-the-headlines machinations behind the trades, the hires and the deals; how the money really works; how the decision making really works; how much power the players really have and why - the real brass tacks of some of the most pivotal decisions made in baseball history that led to great success along with heartbreak and failure on the field. Baseball fans will come for the grit and insight, stay for the heart, and pass it on for the wisdom.https://digitalcommons.pepperdine.edu/facultybooks/1009/thumbnail.jp

    Molnar, Alex, and Joseph A. Reaves, The Growth of Schoolhouse Commercialism and the Assault on Educative Experience, Journal of Curriculum and Supervision, 18(Fall, 2002), 17-55.

    No full text
    Surveys published evidence of intrusion of businesses into educational systems and practices; documents growth in these intrusions over the last two years

    Tunable, Self-curing Polymers for the Forensic Collection of Latent Signatures from Within Porous Materials

    Get PDF
    This article appeared in Homeland Security Affairs (May 2012), supplement 5, article 5"Self-curing polysiloxane polymers have been developed for the forensic collection of latent signatures of explosives, organophosphates, and chemical warfare agent (CWA) degradation products. These polymeric materials penetrate the sample substrate as viscous liquids and subsequently harden to a semi-soft solid that can be peeled away from the substrate to extract signatures via the noncovalent interaction of the newly formed polymeric material with the analytes buried within the substrate. This paper discusses experiments aimed at altering the chemical and physical properties of the polysiloxane sampling materials to optimize signature recovery from porous substrates. The utility of this approach is demonstrated by the collection of target analytes from within concrete. The recovery of these signatures using the self curing polymeric formulations is compared to current operational sampling alternatives such as adhesive fingerprint lifters and swabs. Demonstration of the preparation, extraction, and analytical methods for the detection of the target analytes is also presented.

    Fruit of the Poisonous \u3cem\u3eLemon\u3c/em\u3e Tree: How the Supreme Court Created Offended-Observer Standing, and Why It\u27s Time for It to Go

    Get PDF
    Can individuals who observe what they consider to be offensive government speech or conduct sue to stop it? Typically notā€”absent additional evidence of a direct and particularized injury. Yet in one area of the law, the fundamental requirements of Article III (limiting federal standing to actual ā€œcasesā€ or ā€œcontroversiesā€) are relaxed: the Establishment Clause. At least ten circuits have held that the mere observation of a display containing religious content (the Ten Commandments, a cross, a menorah, and the like) on public property suffices to create an injury-in-fact that opens the doors to federal court. This Essay addresses the continued viability of offended-observer standing after the Supreme Courtā€™s recent decision in American Legion v. American Humanist Association. It picks up on arguments made by Justice Gorsuchā€”and by the Becket Fund for Religious Libertyā€™s amicus brief, which we helped authorā€”explaining why, with the much-criticized Lemon test now ā€œshelved,ā€ it is time for courts to similarly abandon the anomalous offended-observer standing doctrine and bring Establishment Clause standing back into line with both the bedrock requirements of Article III and binding Supreme Court precedent. We first explore the history of offended-observer standing and show how offended-observer standing grew out of overeager efforts by courts of appeals to find an Article III injury that would allow plaintiffs to vindicateā€”in the religious-display contextā€”the substantive Establishment Clause rights created by Lemon. We then argue that it makes no sense to keep applying this relic in a post-Lemon world and explain why offended-observer standing is inconsistent with Supreme Court precedent, the historical meaning of Article III, and judicial prudence

    Fruit of the Poisonous \u3cem\u3eLemon\u3c/em\u3e Tree: How the Supreme Court Created Offended-Observer Standing, and Why It\u27s Time for It to Go

    Get PDF
    Can individuals who observe what they consider to be offensive government speech or conduct sue to stop it? Typically notā€”absent additional evidence of a direct and particularized injury. Yet in one area of the law, the fundamental requirements of Article III (limiting federal standing to actual ā€œcasesā€ or ā€œcontroversiesā€) are relaxed: the Establishment Clause. At least ten circuits have held that the mere observation of a display containing religious content (the Ten Commandments, a cross, a menorah, and the like) on public property suffices to create an injury-in-fact that opens the doors to federal court. This Essay addresses the continued viability of offended-observer standing after the Supreme Courtā€™s recent decision in American Legion v. American Humanist Association. It picks up on arguments made by Justice Gorsuchā€”and by the Becket Fund for Religious Libertyā€™s amicus brief, which we helped authorā€”explaining why, with the much-criticized Lemon test now ā€œshelved,ā€ it is time for courts to similarly abandon the anomalous offended-observer standing doctrine and bring Establishment Clause standing back into line with both the bedrock requirements of Article III and binding Supreme Court precedent. We first explore the history of offended-observer standing and show how offended-observer standing grew out of overeager efforts by courts of appeals to find an Article III injury that would allow plaintiffs to vindicateā€”in the religious-display contextā€”the substantive Establishment Clause rights created by Lemon. We then argue that it makes no sense to keep applying this relic in a post-Lemon world and explain why offended-observer standing is inconsistent with Supreme Court precedent, the historical meaning of Article III, and judicial prudence

    A Systematic Method for the Targeted Discovery of Chemical Attribution Signatures: Application to Isopropyl Bicyclophosphate Production

    No full text
    Potential attribution signatures for the synthesis of a highly toxic bicyclophosphate, 4-isopropyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]Ā­octane 1-oxide (Isopropyl Bicyclophosphate or IPBCP) were discovered using a trilateral synthetic, analytical, and statistical approach. Initially, five synthetic routes were confirmed to successfully produce IPBCP using a range of reaction solvents, reactant ratios, and reaction temperatures. Experimental design principles were subsequently used to guide a formal study specifically aimed at discovering attribution signatures that could be used to differentiate forensic samples. A comparison of three-dimensional scatter plots comprised of the detected ions, their relative retention times (RRTs) and intensities (from LC-MS analyses) identified: (1) signatures that were unique to a synthetic route; (2) signatures associated with a combination of synthetic route and reaction solvent; (3) signatures related to reaction solvent, and (4) signatures associated with reagent source. Top level analysis revealed that the majority of the signatures are related to the synthetic route or a combination of the synthetic route and reaction solvent. Deeper analysis utilizing high resolution mass spectrometry (HRMS) and MS<sup>n</sup> revealed that most of the signatures stem from impurities in the reagents or byproducts formed from incomplete reactions between the reagents used in a given synthetic route. Finally, a subsequent validation study was performed to assess the presence and absence of the key route dependent signatures
    corecore