Organocatalytic Synthesis of Quinine-Functionalized Poly(carbonate)s

Edward, Justin A.,Kiesewetter, Matthew K.,Kim, Hyunuk,Flanagan, James C.A.,Hedrick, James L.,Waymouth, Robert M. American Chemical Society 2012 Biomacromolecules Vol.13 No.8

<P>The ring-opening polymerization of substituted cyclic carbonates with 1-(3,5-bis-trifluoromethyl-phenyl)-3-cyclohexyl-thiourea (TU)/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) organocatalysts afford highly functionalized oligocarbonates. The fluorescent alkaloid quinine can be readily incorporated into the oligocarbonates either by initiation from quinine or by ring-opening polymerization of a quinine-functionalized cyclic carbonate (MTC-Q). Copolymerization of MTC-Q with a boc-protected guanidinium cyclic carbonate affords, after deprotection, highly water-soluble cationic copolymers functionalized with both quinine and pendant guanidinium groups. When multiple quinine groups are attached to the oligomers, they exhibit minimal fluorescence due to self-quenching. Upon hydrolysis, the fluorescence intensity increases, providing a potential strategy for monitoring the hydrolysis rates in real time.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2012/bomaf6.2012.13.issue-8/bm300718b/production/images/medium/bm-2012-00718b_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm300718b'>ACS Electronic Supporting Info</A></P>

DESIGN AND VALIDATION OF ROBUST AND AUTONOMOUS CONTROL FOR NUCLEAR REACTORS

SHAFFER ROMAN A.,EDWARDS ROBERT M.,LEE KWANG Y. Korean Nuclear Society 2005 Nuclear Engineering and Technology Vol.37 No.2

A robust control design procedure for a nuclear reactor has been developed and experimentally validated on the Penn State TRIGA research reactor. The utilization of the robust controller as a component of an autonomous control system is also demonstrated. Two methods of specifying a low order (fourth-order) nominal-plant model for a robust control design were evaluated: 1) by approximation based on the 'physics' of the process and 2) by an optimal Hankel approximation of a higher order plant model. The uncertainty between the nominal plant models and the higher order plant model is supplied as a specification to the ,u-synthesis robust control design procedure. Two methods of quantifying uncertainty were evaluated: 1) a combination of additive and multiplicative uncertainty and 2) multiplicative uncertainty alone. The conclusions are that the optimal Hankel approximation and a combination of additive and multiplicative uncertainty are the best approach to design robust control for this application. The results from nonlinear simulation testing and the physical experiments are consistent and thus help to confirm the correctness of the robust control design procedures and conclusions.

Design and Validation of Robust and Autonomous Control for Nuclear Reactors

ROMAN A. SHAFFER,ROBERT M. EDWARDS,KWANG Y. LEE 한국원자력학회 2005 Nuclear Engineering and Technology Vol.37 No.2

A robust control design procedure for a nuclear reactor has been developed and experimentally validated on the Penn State TRIGA research reactor. The utilization of the robust controller as a component of an autonomous control system is also demonstrated. Two methods of specifying a low order (fourth-order) nominal-plant model for a robust control design were evaluated: 1) by approximation based on the “physics” of the process and 2) by an optimal Hankel approximation of a higher order plant model. The uncertainty between the nominal plant models and the higher order plant model is supplied as a specification to the -synthesis robust control design procedure. Two methods of quantifying uncertainty were evaluated: 1) a combination of additive and multiplicative uncertainty and 2) multiplicative uncertainty alone. The conclusions are that the optimal Hankel approximation and a combination of additive and multiplicative uncertainty are the best approach to design robust control for this application. The results from nonlinear simulation testing and the physical experiments are consistent and thus help to confirm the correctness of the robust control design procedures and conclusions.

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events

Wong, Vanessa K,Baker, Stephen,Pickard, Derek J,Parkhill, Julian,Page, Andrew J,Feasey, Nicholas A,Kingsley, Robert A,Thomson, Nicholas R,Keane, Jacqueline A,Weill, Franç,ois-Xavier,Edwards, Dav Nature Pub. Co 2015 Nature genetics Vol.47 No.6

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.

Polycondensation of Butenediol: Synthesis of Telechelic 2-Butene-1,4-diol Oligomers

Kiesewetter, Matthew K.,Edward, Justin A.,Kim, Hyunuk,Waymouth, Robert M. American Chemical Society 2011 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.133 No.41

<P>The catalytic condensation of <I>cis</I>-2-butene-1,4-diol with CpRu(MQA)(C<SUB>3</SUB>H<SUB>5</SUB>) (Cp = cyclopentadienyl, MQA = 4-methoxyquinoline-2-carboxylate) generates poly(2-butenediol), an unsaturated telechelic polyether diol with molecular weights between 400 and 4600 g/mol. This Ru(IV) allyl catalyst enchains 2-butene-1,4-diol primarily as the linear <I>trans</I>-2-butenyl ether (92%) along with vinyl branches (8%). These telechelic oligomers are useful chain extenders and macromonomers, as demonstrated by their use in the synthesis of poly(lactide)-<I>b</I>-poly(butenediol)-<I>b</I>-poly(lactide) triblock copolymers. Model studies support a proposed mechanism involving the formation of Ru(IV) allyl intermediates from allylic alcohols and chain growth by selective nucleophilic displacement at the terminus of the Ru(IV) allyl to generate <I>trans</I>-2-butenyl ether linkages.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2011/jacsat.2011.133.issue-41/ja207465h/production/images/medium/ja-2011-07465h_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja207465h'>ACS Electronic Supporting Info</A></P>

Orofacial Injury and the Development of Acute PTSD

Glynn, Shirley M.,Asarnow, Joan R.,Robert Asarnow,Vivek Shetty,Elliott Brown, Karin A.,Edward Black,David Forney Korean Academy of Oral Biology and the UCLA Dental 1999 International Journal of Oral Biology Vol.24 No.1

To examine the development of acute post traumatic stress disorder (PTSD) in inner-city, minority patients seeking care for orofacial injury were evaluated. Trained interviewers collected baseline data from one-hundred seventy-two patients seeking care for orofacial injury at an urban trauma center. Follow-up assessments of PTSD (DSM-IV criteria) and perceived impact of the injury on social functioning were repeated at one month post-injury. Patients were predominantly male and largely African-American or Hispanic. At the one month follow-up visit, 52 patients (30%) endorsed symptoms resulting from the facial injury consistent with a PTSD diagnosis. Significant predictors of the development of acute PTSD included older age and perceived life threat at the time of the incident. A substantial subsample of orofacial injury patients presenting to inner-city hospitals has negative psychological outcomes at one-month post-injury. Results underscore the potential utility of screening survivors of orofacial injury at urban trauma centers for PTSD by eliciting responses to a perceived life threat questions and developing systems of care that facilitate referral to appropriate psychological treatment.

Effects of innate immune receptor stimulation on extracellular α-synuclein uptake and degradation by brain resident cells

Kim Changyoun,Kwon Somin,Iba Michiyo,Spencer Brian,Rockenstein Edward,Mante Michael,Adame Anthony,Shin Soo Jean,Fields Jerel A.,Rissman Robert A.,Lee Seung-Jae,Masliah Eliezer 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Synucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in the spread of α-syn pathology, the detailed mechanism is still unknown. Neuroinflammation is another key pathological feature of synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). However, the species of α-syn aggregates varies from study to study, and how different α-syn aggregate species interact with innate immune receptors has yet to be addressed. Therefore, we investigated whether innate immune receptors can facilitate the uptake of different species of α-syn aggregates. Here, we examined whether stimulation of TLRs could modulate the cellular uptake and degradation of α-syn fibrils despite a lack of direct interaction. We observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes. Internalized α-syn was rapidly degraded in microglia regardless of whether TLR2 was stimulated. However, cellular α-syn uptake and degradation kinetics were not altered by TLR4 stimulation. In addition, upregulation of TLR2 expression in a synucleinopathy mouse model increased the density of Lewy-body-like inclusions and induced morphological changes in microglia. Together, these results suggest that cell type-specific modulation of TLR2 may be a multifaceted and promising therapeutic strategy for synucleinopathies; inhibition of neuronal and astroglial TLR2 decreases pathogenic α-syn transmission, but activation of microglial TLR2 enhances microglial extracellular α-syn clearance.

Cyanobacterial biodiversity of semiarid public drinking water supply reservoirs assessed via next-generation DNA sequencing technology

Adriana Sturion Lorenzi,Mathias Ahii Chia,Fabyano Alvares Cardoso Lopes,Genivaldo Gueiros Z. Silva,Robert A. Edwards,Maria do Carmo Bittencourt-Oliveira 한국미생물학회 2019 The journal of microbiology Vol.57 No.6

Next-generation DNA sequencing technology was applied to generate molecular data from semiarid reservoirs during well-defined seasons. Target sequences of 16S-23S rRNA ITS and cpcBA-IGS were used to reveal the taxonomic groups of cyanobacteria present in the samples, and genes coding for cyanotoxins such as microcystins (mcyE), saxitoxins (sxtA), and cylindrospermopsins (cyrJ) were investigated. The presence of saxitoxins in the environmental samples was evaluated using ELISA kit. Taxonomic analyses of high-throughput DNA sequencing data showed the dominance of the genus Microcystis in Mundaú reservoir. Furthermore, it was the most abundant genus in the dry season in Ingazeira reservoir. In the rainy season, 16S-23S rRNA ITS analysis revealed that Cylindrospermopsis raciborskii comprised 46.8% of the cyanobacterial community in Ingazeira reservoir, while the cpcBAIGS region revealed that C. raciborskii (31.8%) was the most abundant taxon followed by Sphaerospermopsis aphanizomenoides (17.3%) and Planktothrix zahidii (16.6%). Despite the presence of other potential toxin-producing genera, the detected sxtA gene belonged to C. raciborskii, while the mcyE gene belonged to Microcystis in both reservoirs. The detected mcyE gene had good correlation with MC content, while the amplification of the sxtA gene was related to the presence of STX. The cyrJ gene was not detected in these samples. Using DNA analyses, our results showed that the cyanobacterial composition of Mundaú reservoir was similar in successive dry seasons, and it varied between seasons in Ingazeira reservoir. In addition, our data suggest that some biases of analysis influenced the cyanobacterial communities seen in the NGS output of Ingazeira reservoir.