bluuebunny/crossref_metadata_2025 huggingface dataset:
Rumen epithelial transcriptome and microbiome profiles of rumen epithelium and contents of beef cattle with and without liver abscesses
Authors: Abbas Waseem , Keel Brittney N , Kachman Stephan D , Fernando Samodha C , Wells James E , Hales Kristin E , Lindholm-Perry Amanda K
Published: November 2020

Abscess is the highest cause of liver condemnation and is estimated to cost the beef industry US$64 million annually. Fusobacterium necrophorum, commonly found in the bovine rumen, is the primary bacteria associated with liver abscess in cattle. Theoretically, damage to the rumen wall allows F. necrophorum to invade the bloodstream and colonize the liver. The objective of this study was to determine the changes in gene expression in the rumen epithelium and microbial populations adherent to the rumen epithelium and in the rumen contents of beef cattle with liver abscesses compared with those with no liver abscesses. Rumen epithelial tissue and rumen content were collected from 31 steers and heifers with liver abscesses and 30 animals with no liver abscesses. Ribonucleic acid (RNA) sequencing was performed on the rumen epithelium, and a total of 221 genes were identified as differentially expressed in the animals with liver abscesses compared with animals with no abscesses, after removal of genes that were identified as a result of interaction with sex. The nuclear factor kappa-light-chain enhancer of activated B cells signaling and interferon signaling pathways were significantly enriched in the differentially expressed gene (DEG) set. The majority of the genes in these pathways were downregulated in animals with liver abscesses. In addition, RNA translation and protein processing genes were also downregulated, suggesting that protein synthesis may be compromised in animals with liver abscesses. The rumen content bacterial communities were significantly different from the rumen wall epimural bacterial communities. Permutational multivariate analysis of variance (PERMANOVA) analysis did not identify global differences in the microbiome of the rumen contents but did identify differences in the epimural bacterial communities on the rumen wall of animals without and with liver abscesses. In addition, associations between DEG and specific bacterial amplicon sequence variants of epimural bacteria were observed. The DEG and bacterial profile on the rumen papillae identified in this study may serve as a method to monitor animals with existing liver abscesses or to predict those that are more likely to develop liver abscesses.
The Impact of NORTH STAR on Suicidality, Substance Problems, Intimate Partner Violence, and Child Abuse
Authors: Slep Amy M Smith , Heyman Richard E , Lorber Michael F , Linkh David J
Published: November 2020

Introduction

We evaluated the effectiveness of New Orientation for Reducing Threats to Health from Secretive-problems That Affect Readiness (NORTH STAR), a community assessment, planning, and action framework to reduce the prevalence of suicidality, substance problems, intimate partner violence, and child abuse.

Materials and Methods

One-third of U.S. Air Force bases worldwide were randomly assigned to NORTH STAR (n = 12) or an assessment-and-feedback-only condition (n = 12). Two Air Force-wide, cross-sectional, anonymous, web-based surveys were conducted of randomly selected samples assessing risk/protective factors and outcomes. This study was reviewed and approved by the institutional review board at the investigators’ university and by the institutional review board at Fort Detrick.

Results

NORTH STAR, relative to control, bases experienced a 33% absolute risk reduction in hazardous drinking rates and cumulative risk, although, given the small number of bases, these effects were not statistically significant.

Conclusions

Given its relatively low cost, use of empirically supported light-touch interventions, and emphasis on sustainability with existing resources, NORTH STAR may be a useful system for prevention of a range of adult behavioral health problems that are difficult to impact.
Double trouble: Gaia reveals (proto)planetary systems that may experience more than one dense star-forming environment
Authors: Schoettler Christina , Parker Richard J
Published: November 2020

Planetary systems appear to form contemporaneously around young stars within young star-forming regions. Within these environments, the chances of survival, as well as the long-term evolution of these systems, are influenced by factors such as dynamical interactions with other stars and photoevaporation from massive stars. These interactions can also cause young stars to be ejected from their birth regions and become runaways. We present examples of such runaway stars in the vicinity of the Orion Nebula Cluster (ONC) found in Gaia DR2 data that have retained their discs during the ejection process. Once set on their path, these runaways usually do not encounter any other dense regions that could endanger the survival of their discs or young planetary systems. However, we show that it is possible for star–disc systems, presumably ejected from one dense star-forming region, to encounter a second dense region, in our case the ONC. While the interactions of the ejected star–disc systems in the second region are unlikely to be the same as in their birth region, a second encounter will increase the risk to the disc or planetary system from malign external effects.
Double-stranded RNA bending by AU-tract sequences
Authors: Marin-Gonzalez Alberto , Aicart-Ramos Clara , Marin-Baquero Mikel , Martín-González Alejandro , Suomalainen Maarit , Kannan Abhilash , Vilhena J G , Greber Urs F , Moreno-Herrero Fernando , Pérez Rubén
Published: November 2020

Sequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. However, in contrast to dsDNA, sequence-dependent structural features of dsRNA have received little attention. In this work, we demonstrate that the nucleotide sequence can induce a bend in a canonical Watson-Crick base-paired dsRNA helix. Using all-atom molecular dynamics simulations, we identified a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that strongly bend the RNA double-helix. This finding was experimentally validated using atomic force microscopy imaging of dsRNA molecules designed to display macroscopic curvature via repetitions of phased AU-tract motifs. At the atomic level, this novel phenomenon originates from a localized compression of the dsRNA major groove and a large propeller twist at the position of the AU-tract. Moreover, the magnitude of the bending can be modulated by changing the length of the AU-tract. Altogether, our results demonstrate the possibility of modifying the dsRNA curvature by means of its nucleotide sequence, which may be exploited in the emerging field of RNA nanotechnology and might also constitute a natural mechanism for proteins to achieve recognition of specific dsRNA sequences.
Structural basis for the substrate specificity and catalytic features of pseudouridine kinase from Arabidopsis thaliana
Authors: Kim Sang-Hoon , Witte Claus-Peter , Rhee Sangkee
Published: November 2020

RNA modifications can regulate the stability of RNAs, mRNA–protein interactions, and translation efficiency. Pseudouridine is a prevalent RNA modification, and its metabolic fate after RNA turnover was recently characterized in eukaryotes, in the plant Arabidopsis thaliana. Here, we present structural and biochemical analyses of PSEUDOURIDINE KINASE from Arabidopsis (AtPUKI), the enzyme catalyzing the first step in pseudouridine degradation. AtPUKI, a member of the PfkB family of carbohydrate kinases, is a homodimeric α/β protein with a protruding small β-strand domain, which serves simultaneously as dimerization interface and dynamic substrate specificity determinant. AtPUKI has a unique nucleoside binding site specifying the binding of pseudourine, in particular at the nucleobase, by multiple hydrophilic interactions, of which one is mediated by a loop from the small β-strand domain of the adjacent monomer. Conformational transition of the dimerized small β-strand domains containing active site residues is required for substrate specificity. These dynamic features explain the higher catalytic efficiency for pseudouridine over uridine. Both substrates bind well (similar Km), but only pseudouridine is turned over efficiently. Our studies provide an example for structural and functional divergence in the PfkB family and highlight how AtPUKI avoids futile uridine phosphorylation which in vivo would disturb pyrimidine homeostasis.
The Association Between Body Mass Index and the Risk of Hospitalization and Mortality due to Infection: A Prospective Cohort Study
Authors: Yang Wei-Shun , Chang Yi-Cheng , Chang Chia-Hsuin , Wu Li-Chiu , Wang Jiun-Ling , Lin Hsien-Ho
Published: November 2020

Background

We aim to determine whether obesity increases the risk of various infections using a large prospective population-based cohort.

Methods

A total of 120 864 adults were recruited from the New Taipei City health screening program from 2005 to 2008. Statistics for hospitalization and mortality due to infection were obtained from the National Health Insurance Database and the National Death Registry in Taiwan.

Results

During a mean follow-up period of 7.61 years, there were 438, 7582, 5298, and 1480 first hospitalizations due to infection in the underweight, normal, overweight, and obese groups, respectively. Obesity significantly increases the risk of hospitalization for intra-abdominal infections (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.00–1.40), including diverticulitis, liver abscess, acute cholecystitis and anal and rectal abscess, reproductive and urinary tract infection (aHR, 1.38; 95% CI, 1.26–1.50), skin and soft tissue infection (aHR, 2.46; 95% CI, 2.15–2.81), osteomyelitis (aHR, 1.70; 95% CI, 1.14–2.54), and necrotizing fasciitis (aHR, 3.54; 95% CI,1.87–6.67), and this relationship is dose-dependent. This study shows that there is a U-shaped association between body mass index (BMI) and hospitalization for lower respiratory tract infection, septicemia, and the summation of all infections and that underweight people are at the greatest risk, followed by obese people. There is a clear negative relationship between BMI and infection-related mortality.

Conclusions

The pattern that BMI affects the risk of hospitalization and mortality due to infection varies widely across infection sites. It is necessary to tailor preventive and therapeutic measures against different infections in hosts with different BMIs.
Functional Group Transformations
Authors: Taber Douglass F.
Published: November 2020

Mark Gandelman of the Technion–Israel Institute of Technology devised (Adv. Synth. Catal. 2011, 353, 1438) a protocol for the decarboxylative conversion of an acid 1 to the iodide 3. Doug E. Frantz of the University of Texas, San Antonio effected (Angew. Chem. Int. Ed. 2011, 50, 6128) conversion of a β-keto ester 4 to the diene 5 by way of the vinyl triflate. Pei Nian Liu of the East China University of Science and Technology and Chak Po Lau of the Hong Kong Polytechnic University (Adv. Synth. Catal. 2011, 353, 275) and Robert G. Bergman and Kenneth N. Raymond of the University of California, Berkeley (J. Am. Chem. Soc. 2011, 133, 11964) described new Ru catalysts for the isomerization of an allylic alcohol 6 to the ketone 7. Xiaodong Shi of West Virginia University optimized (Adv. Synth. Catal. 2011, 353, 2584) a gold catalyst for the rearrangement of a propargylic ester 8 to the enone 9. Xue-Yuan Liu of Lanzhou University used (Adv. Synth. Catal. 2011, 353, 3157) a Cu catalyst to add the chloramine 11 to the alkyne 10 to give 12. Kasi Pitchumani of Madurai Kamaraj University converted (Org. Lett. 2011, 13, 5728) the alkyne 13 into the α-amino amide 15 by reaction with the nitrone 14. Katsuhiko Tomooka of Kyushu University effected (J. Am. Chem. Soc. 2011, 133, 20712) hydrosilylation of the propargylic ether 16 to the alcohol 17. Matthew J. Cook of Queen’s University Belfast (Chem. Commun. 2011, 47, 11104) and Anna M. Costa and Jaume Vilarrasa of the Universitat de Barcelona (Org. Lett. 2011, 13, 4934) improved the conversion of an alkenyl silane 18 to the iodide 19. Vinay Girijavallabhan of Merck/Kenilworth developed (J. Org. Chem. 2011, 76, 6442) a Co catalyst for the Markovnikov addition of sulfide to an alkene 20. Hojat Veisi of Payame Noor University oxidized (Synlett 2011, 2315) the thiol 22 directly to the sulfonyl chloride 23. Nicholas M. Leonard of Abbott Laboratories prepared (J. Org. Chem. 2011, 76, 9169) the chromatography-stable O-Su ester 25 from the corresponding acid 24.
Functional Group Oxidation
Authors: Lambert Tristan H.
Published: November 2020

In a remarkable example of chemoselective oxidation, Scott J. Miller at Yale University identified (Nature Chem. 2012, 4, 990) a peptide catalyst that selectively epoxidized the 6,7-olefin of farnesol 1. Phil S. Baran at Scripps-La Jolla developed (Nature Chem. 2012, 4, 629) the Tz°sulfonate as a “portable desaturase” capable of site-specific C–H functionalization of complex molecules, such as in the conversion of peptide 3 to 4. A unique method for the preparation of α-oxygenated ketones was developed (Angew. Chem. Int. Ed. 2012, 51, 7799) by Laura L. Anderson at the University of Illinois at Chicago. Cross-coupling of cyclohexenyl boronic acid with N-hydroxyphthalimide produced N-enoxyphthalimides 5, which underwent a trihetero [3,3]-sigmatropic rearrangement to produce, after hydrolysis and protection, ketone 6. The enantioselective α-hydroxylation of oxindole 7 with atmospheric O2 catalyzed by pentanidium 8 was reported (Org. Lett. 2012, 14, 4762) by Zhiyong Jiang at Henan University and Choon-Hong Tan at Nanyang Technological University. A catalytic Baeyer-Villiger oxidation of ketones such as 10 using highly reactive metal borate salts was developed (Angew. Chem. Int. Ed. 2012, 51, 9093) by Kazuaki Ishihara at Nagoya University. Masatoshi Shibuya and Yoshiharu Iwabuchi at Tohoku University found (Org. Lett. 2012, 14, 5010) that nitroxyl radicals such as 13 catalyzed the oxidative cleavage of diols to carboxylic acids, such as in the conversion of 12 to 14. A highly reactive iridium catalyst 16 was reported (Angew. Chem. Int. Ed. 2012, 51, 12790) by Ken-ichi Fujita and Ryohei Yamaguchi at Kyoto University, which had high turnover numbers under mild conditions for the oxidation of alcohols including 15. Frank W. Foss Jr. at the University of Texas at Arlington developed (Org. Lett. 2012, 14, 5150) a biomimetic Dakin oxidation of electron-rich aryl aldehydes such as 18, using the flavin-type catalyst 19, Hantzsch ester, and oxygen as the terminal oxidant. Flavin-catalyzed oxidation of aldehydes using catalyst 22 was also reported (Org. Lett. 2012, 14, 3656) by David R. Carbery at the University of Bath. Carlos F. Barbas III at Scripps-La Jolla developed (Angew. Chem. Int. Ed. 2012, 51, 12538) a catalytic conversion of aldehydes such as 24 to the corresponding O-acyl N-hydroxyimides (cf. 25), which could be used for in situ amidations and esterifications.
Flow Chemistry
Authors: Lambert Tristan H.
Published: November 2020

Although photocatalytic chemistry has been the subject of intense interest recently, the rate of these reactions is often slow due to the limited penetration of light into typical reaction media. Peter H. Seeberger at the Max-Planck Institute for Colloids and Surfaces in Potsdam and the Free University of Berlin showed (Chem. Sci. 2012, 3, 1612) that Ru(bpy)32+-catalyzed reactions such as the reduction of azide 1 to 2 can be achieved in as little as 1 min residence time using continuous flow, as opposed to the 2 h batch reaction time previously reported. The benefits of flow on a number of strategic photocatalytic reactions, including the coupling of 3 and 4 to produce 5, was also demonstrated (Angew. Chem. Int. Ed. 2012, 51, 4144) by Corey R.J. Stephenson at Boston University and Timothy F. Jamison at MIT. In this case, a reaction throughput of 0.914 mmol/h compares favorably with 0.327 mmol/h for the batch reaction. Professor Seeberger has also reported (Angew. Chem. Int. Ed. 2012, 51, 1706) a continuous-flow synthesis of Artemisinin 7, a highly effective antimalarial drug, starting from dihydroartemisinic acid 6. The conversion occurs by a sequence of photochemical oxidation with singlet oxygen, acidic Hock cleavage of the O–O bond, and oxidation with triplet oxygen, a process calculated to be capable of furnishing up to 200 g/day per reactor. A scalable intramolecular [2 + 2] photocycloaddition of 8 to produce 9 was reported (Tetrahedron Lett. 2012, 53, 1363) by Matthias Nettekoven of Hoffmann-La Roche in Basel, Switzerland. Stephen L. Buchwald at MIT developed (Angew. Chem. Int. Ed. 2012, 51, 5355) a flow process for the enantioselective β-arylation of ketones that involved lithiation of aryl bromide 10, borylation, and rhodium-catalyzed conjugate addition to cycloheptenone. For continuous flow production of enantioenriched alcohols such as 14, Miquel A. Pericás of the Institute of Chemical Research of Catalonia developed (Org. Lett. 2012, 14, 1816) the robust polystyrene-supported aminoalcohol 13 for diethylzinc addition to aldehydes. Professor Jamison found (Org. Lett. 2012, 14, 568) that flow chemistry provides a convenient and reliable solution to the reduction of esters to aldehydes with DIBALH (e.g., 15 to 16) that occurs rapidly and without the usual problem of overreduction.
C–H Functionalization: The Ono/Kato/Dairi Synthesis of Fusiocca-1,10(14)-diene-3,8β,16-triol
Authors: Taber Douglass F.
Published: November 2020

Theodore A. Betley of Harvard University devised (J. Am. Chem. Soc. 2011, 133, 4917) an iron catalyst for inserting the nitrene from 2 into the C–H of 1 to give 3. Bernhard Breit of the Freiburg Institute for Advanced Studies uncovered (J. Am. Chem. Soc. 2011, 133, 2386) a Rh catalyst that effected the intriguing hydration of a terminal alkyne 4 to the allylic ester 5. Yian Shi of Colorado State University specifically oxidized (Org. Lett. 2011, 13, 1548) one of the two allylic sites of 6 to give 7. Kálmán J. Szabó of Stockholm University optimized (J. Org. Chem. 2011, 76, 1503) the allylic oxidation of 9 to 10, using the inexpensive sodium perborate. Masayuki Inoue of the University of Tokyo specifically carbamoylated (Tetrahedron Lett. 2011, 52, 2885) the acetonide 12 to give 14. Stephen Caddick of University College London added (Tetrahedron Lett. 2011, 52, 1067) the formyl radical from 15 to 16 to give 17. Ilhyong Ryu of Osaka Prefecture University and Maurizio Fagnoni of the University of Pavia employed (Angew. Chem. Int. Ed. 2011, 50, 1869) a related strategy to effect the net transformation of 18 to 20. There are many examples of the oxidation of ethers and amines to reactive intermediates that can go on to carbon–carbon bond formation. Ram A. Vishwakarma of the Indian Institute of Integrative Medicine observed (Chem. Commun. 2011, 47, 5852) that with an iron catalyst, the aryl Grignard 22 smoothly coupled with THF 21 to give 23. Gong Chen of Pennsylvania State University effected (Angew. Chem. Int. Ed. 2011, 50, 5192) specific remote C–H arylation of 24, leading to 26. Takahiko Akiyama of Gakushuin University established (J. Am. Chem. Soc. 2011, 133, 2424) conditions for intramolecular hydride abstraction, effecting the conversion of 27 to 28. C–H functionalization in nature is often mediated by cytochrome P450 oxidation. Zhi Li of the National University of Singapore showed (Chem. Commun. 2011, 47, 3284) that a particular cytochrome P450 selectively oxidized 29 to the alcohol 30, leaving the chemically more reactive benzylic position intact.
Enantioselective Construction of Alkylated Centers: The Shishido Synthesis of (+)-Helianane
Authors: Taber Douglass F.
Published: November 2020

Teck-Peng Loh of Nanyang Technological University developed (Org. Lett. 2011, 13, 876) a catalyst for the enantioselective addition of an aldehyde to the versatile acceptor 2 to give 3. Kirsten Zeitler of the Universität Regensburg employed (Angew. Chem. Int. Ed. 2011, 50, 951) a complementary strategy for the enantioselective coupling of 4 with 5. Clark R. Landis of the University of Wisconsin devised (Org. Lett. 2011, 13, 164) an Rh catalyst for the enantioselective formylation of the diene 7. Don M. Coltart of Duke University alkylated (J. Am. Chem. Soc. 2011, 133, 8714) the chiral hydrazone of acetone to give 9, then alkylated again to give, after hydrolysis, the ketone 11 in high ee. Youming Wang and Zhenghong Zhou of Nankai University effected (J. Org. Chem. 2011, 76, 3872) the enantioselective addition of acetone to the nitroalkene 12. Takeshi Ohkuma of Hokkaido University achieved (Angew. Chem. Int. Ed. 2011, 50, 5541) high ee in the Ru-catalyzed hydrocyanation of 15. Gregory C. Fu, now at the California Institute of Technology, coupled (J. Am. Chem. Soc. 2011, 133, 8154) the 9-BBN borane 18 with the racemic chloride 17 to give 19 in high ee. Scott McN. Sieburth of Temple University optimized (Org. Lett. 2011, 13, 1787) an Rh catalyst for the enantioselective intramolecular hydrosilylation of 20 to 21. Several general methods have been devised for the enantioselective assembly of quaternary alkylated centers. Sung Ho Kang of KAIST Daejon developed (J. Am. Chem. Soc. 2011, 133, 1772) a Cu catalyst for the enantioselective acylation of the prochiral diol 22. Hyeung-geun Park of Seoul National University established (J. Am. Chem. Soc. 2011, 133, 4924) a phase transfer catalyst for the enantioselective alkylation of 24. Peter R. Schreiner of Justus-Liebig University Giessen found (J. Am. Chem. Soc. 2011, 133, 7624) a silicon catalyst that efficiently rearranged the Shi-derived epoxide of 26 to the aldehyde 27. Amir H. Hoveyda of Boston College coupled (J. Am. Chem. Soc. 2011, 133, 4778) 28 with the alkynyl Al reagent 29 to give 30 in high ee. Kozo Shishido of the University of Tokushima prepared (Synlett 2011, 1171) 31 by the Mitsunobu coupling of m-cresol with the enantiomerically pure allylic alcohol.
Total Synthesis of C–O Ring-Containing Natural Products
Authors: Lambert Tristan H.
Published: November 2020

Scott A. Snyder at Columbia University demonstrated (J. Am. Chem. Soc. 2012, 134, 17714) that tetrahydrofuran 1 could be readily converted to oxocane 2 by treatment with the BDSB reagent developed in his laboratory. Reduction of 2 with DIBAL-H initiated a second ring closure by mesylate displacement to form the bicycle 3, which represented a formal total synthesis of laurefucin 4. Andrew L. Lawrence at the Australian National University found (Org. Lett. 2012, 14, 4537) that upon treatment with catalytic base, rengyolone 6, which was prepared in one pot from phenol 5, could be converted to the natural products incarviditone 7 and incarvilleatone 8. This demonstration provides strong support for the postulated biomimetic formation of these natural products. Shuanhu Gao at East China Normal University reported (Angew. Chem. Int. Ed. 2012, 51, 7786) the total synthesis of (+)-fusarisetin A 12 via biomimetic oxidation of equisetin 10 to produce the peroxy compound 11, followed by reduction. The bicyclic carbon skeleton of equisetin 10 was synthesized by intramolecular Diels-Alder reaction of trienyl aldehyde 9. The ellagitannin natural product (+)-davidiin 15 possesses a glucopyranose core with the unusual 1C4 (tetraaxial) conformation due to the presence of a biaryl bridge between two of the galloyl groups. Hidetoshi Yamada at Kwansei Gakuin University constructed (Angew. Chem. Int. Ed. 2012, 51, 8026) this bridge by oxidation with CuCl2 of 13, in which the three sterically demanding triisopropylsiloxy groups enforce the requisite tetraaxial conformation. John A. Porco, Jr. at Boston University applied (J. Am. Chem. Soc. 2012, 134, 13108) his asymmetric [3+2] photocycloaddition chemistry to the total synthesis of the aglain natural product (+)-ponapensin 20. Irradiation of hydroxyflavone 16 with methyl cinnamate 17 in the presence of diol 18 afforded the entire core framework 19 of ponapensin 20, which was accessed in just a few further synthetic transformations. Finally, Silas P. Cook at Indiana University reported (J. Am. Chem. Soc. 2012, 134,13577) a five-pot total synthesis of the antimalarial (+)-artemisinin 25. Cyclohexenone 21 was converted by simple operations to aldehyde 22. This aldehyde was then engaged in a [4+2] cycloaddition with the silyl ketene acetal 23 to produce, after an impressive Wacker oxidation of the disubstituted olefin, bicycle 24.
C–N Ring Construction: The Hoye Synthesis of (±)-Leuconolactam
Authors: Taber Douglass F.
Published: November 2020

Manas K. Ghorai of the Indian Institute of Technology, Kanpur depended (J. Org. Chem. 2013, 78, 2311) on memory of chirality during deprotonation to convert 1 to the aziridine 3. X. Peter Zhang of the University of South Florida demonstrated (Angew. Chem. Int. Ed. 2013, 52, 5309) that Co-catalyzed enantioselective aziridination is compatible with fluoro-aromatics such as 5. David M. Hodgson of the University of Oxford prepared (J. Org. Chem. 2013, 78, 1098) the azetidine 8 by double deprotonation of 7 followed by acylation. Laurel L. Schafer of the University of British Columbia assembled (Org. Lett. 2013, 15, 2182) 11 by Ta-catalyzed aminoalkylation of 10 with 9, followed by cyclization. Nicholas A. Magnus of Eli Lilly reduced (J. Org. Chem. 2013, 78, 5768) the ketone 12 to the alcohol 13 with high de and ee. Pei-Qiang Huang of Xiamen University effected (J. Org. Chem. 2013, 78, 1790) the reductive addition of 14 to 15 to give 16. The titanocene protocol reported (Angew. Chem. Int. Ed. 2013, 52, 3494) by Xiao Zheng, also of Xiamen University, effectively mediated similar transformations. En route to (–)-quinocarcin, Nobutaka Fujii and Hiroaki Ohno of Kyoto University cyclized (Chem. Eur. J. 2013, 19, 8875) 17 to 18 with high diastereoselectivity. Dipolar cycloaddition, long a workhorse of pyrrolidine synthesis, has been improved by enantioselective organocatalysis. For instance, Liu-Zhu Gong of the University of Science and Technology of China combined (Org. Lett. 2013, 15, 2676) 19, 20, and 21 to give the triester 22. Qi-Lin Zhou of Nankai University reduced (Angew. Chem. Int. Ed. 2013, 52, 6072) the tetrahydropyridine 23 to 24 in high ee. Takaaki Sato and Noritaka Chida of Keio University cyclized (Chem. Eur. J. 2013, 19, 678) the intermediate from reduction of 25 to the piperidine 26. Yasumasa Hamada of Chiba University devised (Tetrahedron Lett. 2013, 54, 1562) the rearrangement of 27 to the piperidine 28. In a synthesis of (–)-hippodamine, Shigeo Katsumura of Kwansei Gakuin University used (Org. Lett. 2013, 15, 2758) the chiral auxiliary 29 to direct the combination of 30 with 31 to give 32.
The Nicolaou/Li Synthesis of Tubingensin A
Authors: Taber Douglass F.
Published: November 2020

The complex indole diterpene alkaloids, isolated both from Aspergillus sp. and from Eupenicillium javanicum, display a wide range of physiological activity. K.C. Nicolaou of Scripps/La Jolla and Ang Li, now at the Shanghai Institute of Organic Chemistry, conceived (J. Am. Chem. Soc. 2012, 134, 8078) a divergent strategy for the assembly of these alkaloids that enabled syntheses of both anominine (not illustrated) and tubingensin A 3. A key step in the assembly of the carbocyclic skeleton of both alkaloids was the radical cyclization of 1 to 2, establishing the second of the two alkylated quaternary centers of 3. The starting point for the preparation of 1 was commercial pulegone 4. Methylation followed by acid-mediated retro aldol condensation delivered the enantiomerically pure 2,3-dimethyl cyclohexanone 5. To maximize yield, the subsequent Robinson annulation was carried out over three steps, formation of the silyl enol ether, condensation of the enol ether with methyl vinyl ketone 6, and base-mediated cyclization and dehydration of the 1,5-diketone to give 7. The secondary hydroxyl group was introduced by exposure to Oxone of the methyl dienol ether derived from 7. The mixture of diastereomers from the radical Ueno-Stork cyclization of 1 was equilibrated to the more stable 2 by exposure to acid. The authors took advantage of the regioselective enolization of 2, preparing the silyl enol ether, which could then be condensed with formaldehyde to give 10. This hydroxy ketone was carried onto 11 over four steps, commencing with silylation and proceeding through Wittig condensation, desilylation, and oxidation. The addition of the Grignard reagent 12 to the aldehyde 11 gave a secondary alcohol, which was readily dehydrated to the diene 13. The diene resisted thermal cyclization, but on exposure to CuOTf at room temperature it was smoothly cyclized and oxidized to 14. The elaboration of the sidechain had already been worked out in the anominine synthesis. The free lactol derived from 14 resisted many nucleophiles, but vinyl magnesium bromide did add. Bis acetylation of the resulting diol followed by Pd-mediated ionization and reduction of the allylic acetate, and reductive removal of the residual acetate, delivered the terminal alkene 15. Metathesis with isobutylene gave 16, which was deprotected to give tubingensin A 3.
Comparing the Paths of the Council on Environmental Quality and the Environmental Protection Agency and Assessing the Life Cycle Models
Authors: Conant James K. , Balint Peter J.
Published: November 2020

In Chapters 4 and 5, we used four organizational life cycle models to develop predictions for the trajectories of the Council on Environmental Quality (CEQ) and the Environmental Protection Agency (EPA)’s appropriations over the forty-year period from their births in 1970 through 2010. In this chapter, we review findings from our studies of the CEQ and EPA, and we offer a general assessment of the power of the theoretical agency life cycle models. We also employ a framework we developed for comparing the models and for classifying the key variables in those models. This framework provides a means to move beyond the constraints of the existing literature, in which life cycle models are placed in either the “internalist” or “externalist” camps. We framed our study of the CEQ and EPA with two general views of what happens to public organizations during the process of implementing public law. One view is that the life of the executive branch organization will be relatively stable and untroubled as its leaders and professional staff pursue the organization’s statutorily assigned mission. The underlying presumption here is that all of the important political questions related to the tasks assigned to the agency have been addressed in the public law itself. Consequently, the work of the agencies will be largely technical and uncontroversial. The alternative view is that the political struggle over the passage of the laws the agencies are supposed to implement continues during the implementation stage of the policymaking process. The supporters of the law, inside and outside government, support the agency and its efforts. The opponents of the law, however, not only oppose the agency but also attempt to derail, or at least delay implementation of, the law. Thus, an agency’s trajectory over time, in the form of its resources for and vigor in support of its assigned implementation tasks, will depend in large part on the balance of power, inside and outside government, between those who support and oppose the agency.
Chemical Mechanisms for Air Quality Modeling and Their Applications
Authors: Calvert Jack G. , Orlando John J. , Stockwell William R. , Wallington Timothy J.
Published: November 2020

A chemical mechanism is a critical component of an air quality model. Tropospheric gas phase chemical mechanisms for air quality modeling are designed to simulate the production of ozone, acids, and aerosol precursors. Therefore, their focus is on the oxidation chemistry of ozone, nitrogen oxides, sulfur compounds, and organic compounds. Figure IX-A-1 is an overview of the most important cycles of radicals that must be represented in a chemical mechanism for air quality modeling. The processes shown schematically on one level may appear to be relatively simple, but, in reality, the chemical mechanism is extremely complicated due to the very large number of organic compounds present in the atmosphere. Atmospheric chemistry mechanisms are based on laboratory data and tested against environmental experiments and field measurements (Stockwell et al., 2012). Usually, the mechanism is considered to consist of chemical species and their reactions and rate coefficients, along with the photochemical data (used to calculate photolysis frequencies). An atmospheric chemical mechanism employed in an air quality model could be considered to include the rules for aggregating emissions and initial concentrations into species (Middleton et al., 1990). There are many thousands of volatile organic compounds (VOCs) emitted into the atmosphere, and each has its own decomposition mechanism that determines the effect of the VOC on ozone production. It is critical for a chemical mechanism to characterize the chemistry of the VOCs and their differences in chemical reactivity as accurately as possible. Middleton et al. (1990) pointed out that air quality models have only a limited number of species compared to emission inventories. An emissions aggregation scheme is the process of mapping a detailed emissions inventory into the limited number of species used in an air quality model. The scheme is an important component of any model chemical mechanism. Middleton et al. published their aggregation process for the mechanism used in the Regional Acid Deposition Model (RADM2, Stockwell et al., 1990), but, too often, the emissions aggregation scheme for a given chemical mechanism is in the gray literature and difficult to access.
Incorporating Neuroimaging into Cognitive Assessment
Authors: Bigler Erin D.
Published: November 2020

All traditional neuropsychological assessment techniques emerged in an era prior to modern neuroimaging. In fact, question-answer/paper-and-pencil test origins that gained traction with Alfred Binet in 1905 remain the same core techniques today. Indeed, Binet’s efforts began the era of standardized human metrics designed to assess a broad spectrum of cognitive, emotional, and behavioral functions and abilities. During the early part of the 20th century, the concept of an intellectual quotient expressed as a standard score with a mean of 100 and a standard deviation of 15 also initiated the era of quantitative descriptions of mental and emotional functioning (Anastasi, 1968; Stern, 1912). Other descriptive statistical metrics were applied to human measurement, including scaled, percentile, T-score, and z-score statistics. Statistical measures became part of the assessment lexicon and each possessed strength as well as weakness for descriptive purposes, but together proved to be immensely effective for communicating test findings and inferring average and above or below the norm performances. In turn, descriptive statistical methods became the cornerstone for describing neuropsychological findings, typically reported by domain of functioning (memory, excutive, language, etc.; Cipolotti & Warrington, 1995; Lezak, Howieson, Bigler, & Tranel, 2012). As much as psychology and medicine have incorporated descriptive statistics into research and clinical application, a major focus of both disciplines also has been binary classification—normal versus abnormal. This dichotomization recognizes some variability and individual differences within a test score or laboratory procedure, but at some point the clinician makes the binary decision of normal or abnormal. In the beginnings of neuroimaging, which are discussed more thoroughly below, interpretation of computed tomographic (CT) or magnetic resonance imaging (MRI) scans mostly was approached in this manner. Although lots of information was available from CT and MRI images, if nothing obviously abnormal was seen, the radiological conclusion merely stated in the Impression section, “Normal CT (or MRI) of the brain,” with no other qualification (or quantification) of why the findings were deemed normal other than the image appeared that way. Until recently, quantification of information in an image required hand editing and was excruciatingly time consuming.
Places Close to Our Hearts
Authors: Toal Gerard
Published: November 2020

When U.S. President George W. Bush first met Russian president Vladimir Putin, he praised him as “an honest, straightforward man who loves his country.” Bush indicated that, more than a decade after the Cold War ended, it was “time to move beyond suspicion and towards straight talk.” Thereafter, both presidents established a good working relationship based, in part, on candor and frankness. Putin’s speech at the Munich security conference did not please his hosts, but it had the virtue of clarifying important differences. Similarly, his speech to the North Atlantic Treaty Organization (NATO)–Russia Council meeting in Bucharest was forthright and blunt. The compromise language of the Bucharest Declaration—Georgia and Ukraine “will become members of NATO”—was a personal rebuke to the Russian leader, for he had made it clear that NATO expansion to these countries was a “red line” for Russia. Two years earlier Russian foreign minister Sergey Lavrov warned publicly that Georgia and Ukraine joining NATO could lead to “a collossal shift in global geopolitics.” But those promoting NATO membership for both believed the Russian position amounted to anachronistic sphere-of-influence thinking, and they were determined to prevent what they described as a “Russian veto” on NATO expansion. Putin’s remarks on Georgia in Bucharest—discussed in chapter 4—attracted few headlines. His alleged comments on Ukraine, however, were viewed with alarm at the time by some and considered ominously prophetic by many after 2008, and especially so in the spring of 2014. According to an unnamed NATO country official, an irate Putin turned to Bush and said: “George, you do realize that Ukraine is not even a state. What is Ukraine? Part of its territory is Eastern Europe but the greater part is a gift from us!” Putin reportedly then indicated that should Ukraine join NATO, the state may cease to exist. Russia would then tear off Crimea and eastern Ukraine from the rest of the country. Six years later it appeared Russia was doing precisely this.
Introduction
Authors: McMichael Anthony
Published: November 2020

Trends In Global Greenhouse emissions during the first two de­cades of this twenty- first century are leading us to a much hotter world by 2100, perhaps 3°C– 4°C above the late- twentieth- century average temperature and hotter than at any time in the last 20– 30 million years. Further, the rate of heating would be about 30 times faster than when Earth emerged from the most recent ice age, between 17,000 and 12,000 years ago. At that speed, environ­mental changes may outstrip the capacity of many species to evolve and adapt. Having once relied on fires in caves, humans in the late eighteenth and nineteenth centuries increasingly began to burn fossil fuels to release vastly more energy— and, inadvertently, vastly more carbon dioxide. About 600 billion metric tons of that invisible, stable, and odorless gas have been emitted since 1750, about two- thirds of which will persist in the atmosphere for centuries. The resulting 40 percent increase in atmospheric carbon dioxide concentration is the main cause of human- driven climate change. We have wrapped another heat- retaining blanket around the planet, causing warming of Earth’s surface at a rate that far outpaces nature’s rhythms. Humans have lived in climatically congenial times for the past 11,000 years of the Holocene geological epoch compared with the rigors of the preceding ice age. Figure 1.1 shows the world’s estimated aver­age surface temperature over that era, and the right- hand side of the graph shows the likely global warming by 2100 averaged across many published modeled projections. The difference between the peak tem­perature of 7,000 years ago and the nadir of the Little Ice Age 350 years ago is 0.7°C. By early in this twenty- first century, the global average temperature had edged higher than for the past 11,000 years— by 0.6°C in six decades. If the world’s temperature were to rise by 3°C– 4°C within just three generations, our descendants might struggle to remain healthy, raise families, and survive within stable societies. I am certainly not the first to say this … A 4°C temperature increase probably means a global carrying capacity below 1 billion people.
Assessing Information Assessments
Authors: Lupia Arthur
Published: November 2020

While many analysts use PK scales to make claims about what people know and why it matters, others use subjective interviewer assessments. The ANES is a common source of these assessments. The ANES asks its interviewers to offer “a five-level summary evaluation of each respondent’s level of information level.” Interviewers rate each respondent as “very high,” “high,” “average,” “fairly low,” or “very low.” Data from these assessments appear in widely cited academic articles on political ignorance. In one such article, Bartels (1996: 203) argues that this variable’s use is preferable to PK scales. He claims that interviewer assessments are . . . no less (and sometimes more) strongly related than factual information scales are to relevant criterion values such as political interest, education, registration, and turnout (Zaller 1985: 4). Given the added difficulty of making comparisons from one election year to another using scales based on rather different sets of available information items of variable quality, the simpler interviewer ratings seem preferable for my purposes here. . . . Other scholars have augmented the case for using interviewer assessments in attempts to understand the relationship between knowledge and other factors. As Claassen and Highton (2006: 415) write: . . . To measure political information, we rely on NES interviewer ratings of respondents’ levels of political information. This indicator has two primary virtues. First, it is present in each of the surveys we analyze providing a consistent measure across survey years. Second, it has proven to be a valid measure. Bartels used it to provide important insights into public opinion toward … information effects in presidential voting (Bartels, 1996). Given our focus on changing information effects over time, we share the view that because of the “added difficulty of making comparisons from one election year to another using scales based on rather different sets of available information items of variable quality, the simpler interviewer ratings seem preferable.” . . . In a footnote (2006: 415n), they continue the argument: . . . For the purposes of this paper, we also prefer the interviewer rating to measures of policy specific information. . . .
Stories From the Leopold Shack
Authors: Leopold Estella B.
Published: November 2020

In 1934, conservationist Aldo Leopold and his wife Estella bought a barn - the remnant of a farm - and surrounding lands in south-central Wisconsin. The entire Leopold clan - five children in all - worked together to put into practice Aldo's "land ethic," which involved ecological restoration and sustainability. In the process, they built more than a pleasant weekend getaway; they established a new way of relating to nature. In 1948, A Sand County Almanac was published, and it has become a beloved and foundational text of the conservation movement. Decades later, Estella B. Leopold, the youngest of the Leopold children - she was eight when they bought the land - now reflects on the "Shack," as they called the repurposed barn, and its inhabitants, and recalls with clear-eyed fondness the part it played in her and her siblings' burgeoning awareness of nature's miracles, season by season. In Stories from the Leopold Shack: Sand County Revisited, she unforgettably recalls the intensity of those days: the taste of fresh honey on sourdough pancakes; the trumpeting arrival of migrating Canada geese; the awesome power of river ice driven by currents - and each description is accompanied by stunning photographs by her brother, A. Carl Leopold. As the Leopolds worked to restore degraded farmland back to its original prairie and woods, they noted and celebrated all of the flora and fauna that came to share the Shack lands. As first evoked in A Sand County Almanac, and now revisited in Stories from the Leopold Shack, the Leopold family's efforts of ecological restoration were among the earliest in the United States, and their work, collectively and individually, continues to have a profound impact on land management and conservationism. All of Aldo and Estella Leopold's children went on to become distinguished scientists and to devote themselves to a life of conservation; their work continues through the Aldo Leopold Foundation. Estella B. Leopold book offers a voyage back to the place where it all began.
The Contemporary US Energy System Overview Including A Comparison With China
Authors: McElroy Michael B.
Published: November 2020

The discussion in chapter 2 addressed what might be described as a microview of the US energy economy— how we use energy as individuals, how we measure our personal consumption, and how we pay for it. We turn attention now to a more expansive perspective— the use of energy on a national scale, including a discussion of associated economic benefits and costs. We focus specifically on implications for emissions of the greenhouse gas CO2. If we are to take the issue of human- induced climate change seriously— and I do— we will be obliged to adjust our energy system markedly to reduce emissions of this gas, the most important agent for human- induced climate change. And we will need to do it sooner rather than later. This chapter will underscore the magnitude of the challenge we face if we are to successfully chart the course to a more sustainable climate- energy future. We turn later to strategies that might accelerate our progress toward this objective.We elected in this volume to focus on the present and potential future of the energy economy of the United States. It is important to recognize that the fate of the global climate system will depend not just on what happens in the United States but also to an increasing extent on what comes to pass in other large industrial economies. China surpassed the United States as the largest national emitter of CO2 in 2006. The United States and China together were responsible in 2012 for more than 42% of total global emissions. Add Russia, India, Japan, Germany, Canada, United Kingdom, South Korea, and Iran to the mix (the other members of the top 10 emitting countries ordered in terms of their relative contributions), and we can account for more than 60% of the global total. Given the importance of China to the global CO2 economy (more than 26% of the present global total and likely to increase significantly in the near term), I decided that it would be instructive to include here at least some discussion of the situation in China— to elaborate what the energy economies of China and the United States have in common, outlining at the same time the factors and challenges that set them apart.