bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing foreground removal techniques for recovery of the LOFAR-EoR 21 cm power spectrum
Authors: Hothi Ian , Chapman Emma , Pritchard Jonathan R , Mertens F G , Koopmans L V E , Ciardi B , Gehlot B K , Ghara R , Ghosh A , Giri S K , Iliev I T , Jelić V , Zaroubi S
Published: November 2020

We compare various foreground removal techniques that are being utilized to remove bright foregrounds in various experiments aiming to detect the redshifted 21 cm signal of neutral hydrogen from the epoch of reionization. In this work, we test the performance of removal techniques (FastICA, GMCA, and GPR) on 10 nights of LOFAR data and investigate the possibility of recovering the latest upper limit on the 21 cm signal. Interestingly, we find that GMCA and FastICA reproduce the most recent 2σ upper limit of $\Delta ^2_{21} \lt $ (73)2 mK2 at k = 0.075 hcMpc−1, which resulted from the application of GPR. We also find that FastICA and GMCA begin to deviate from the noise-limit at k-scales larger than ∼0.1 hcMpc−1. We then replicate the data via simulations to see the source of FastICA and GMCA’s limitations, by testing them against various instrumental effects. We find that no single instrumental effect, such as primary beam effects or mode-mixing, can explain the poorer recovery by FastICA and GMCA at larger k-scales. We then test scale-independence of FastICA and GMCA, and find that lower k-scales can be modelled by a smaller number of independent components. For larger scales (k ≳ 0.1 hcMpc−1), more independent components are needed to fit the foregrounds. We conclude that, the current usage of GPR by the LOFAR collaboration is the appropriate removal technique. It is both robust and less prone to overfitting, with future improvements to GPR’s fitting optimization to yield deeper limits.
First estimations of gravity wave potential energy in the Martian thermosphere: an analysis using MAVEN NGIMS data
Authors: Manju G , Mridula N
Published: November 2020

First estimations of Gravity Wave Potential Energy (GWPE) for Martian thermosphere are reported herein using the height profile of CO2 density derived temperature fluctuations for different Martian seasons during the 33rd Martian year. Explicit diurnal evolution of GWPE (52⁰ to 73⁰ latitude bin) with a post sunset maximum is delineated for summer. The higher values of GWPE are observed during morning, compared to post-midnight (35⁰ to 55⁰ latitude bin) for summer. As latitude increases from 16⁰ to 45⁰, GWPE (1-4 LT bin) is found to be nearly doubled for summer. Further, GWPE estimates in autumn are 6 times higher during night compared to day (-45⁰ to -72⁰ latitude bin) and day time (-53⁰ to -72⁰ latitude bin) GWPE is much lower in autumn compared to spring for all longitudes. Overall, from the available data, southern autumn daytime periods appear better suited for aero-braking operations of Martian landing missions.
The function of RAD52 N-terminal domain is essential for viability of BRCA-deficient cells
Authors: Hanamshet Kritika , Mazin Alexander V
Published: November 2020

RAD52 is a member of the homologous recombination pathway that is important for survival of BRCA-deficient cells. Inhibition of RAD52 leads to lethality in BRCA-deficient cells. However, the exact mechanism of how RAD52 contributes to viability of BRCA-deficient cells remains unknown. Two major activities of RAD52 were previously identified: DNA or RNA pairing, which includes DNA/RNA annealing and strand exchange, and mediator, which is to assist RAD51 loading on RPA-covered ssDNA. Here, we report that the N-terminal domain (NTD) of RAD52 devoid of the potential mediator function is essential for maintaining viability of BRCA-deficient cells owing to its ability to promote DNA/RNA pairing. We show that RAD52 NTD forms nuclear foci upon DNA damage in BRCA-deficient human cells and promotes DNA double-strand break repair through two pathways: homology-directed repair (HDR) and single-strand annealing (SSA). Furthermore, we show that mutations in the RAD52 NTD that disrupt these activities fail to maintain viability of BRCA-deficient cells.
Methylenedioxymethamphetamine (MDMA)a.k.a. Ecstasy
Authors: Winter Jerrold
Published: November 2020

As these words are written, the chemical we will call MDMA is a Schedule I drug. This means that MDMA (a) has no currently accepted medical use, (b) no currently accepted safety even under medical supervision, and (c) has a high potential for abuse. On the other hand, there are those who see great therapeutic potential in MDMA, and the Food and Drug Administration (FDA) has designated MDMA- assisted psychotherapy as a breakthrough therapy. We can foresee the day when it will be available by prescription. There is no doubt as to the chemical identity of MDMA, and much is known of its pharmacological effects in humans and in animals. The recreational drug commonly known as Ecstasy is more complicated. As is true for any illegal drug used by millions of people, demand for the drug has been met by persons not noted for their high ethical or manufacturing standards. Simply stated, short of chemical analysis, one can never be sure what street-bought Ecstasy is. For example, investigators at Vanderbilt University determined the contents of 1,214 tablets sold as Ecstasy. Only 39% contained only MDMA, while fully 46% were “substances other than MDMA.” Mixtures of MDMA and other drugs comprised the remaining 15%. On the other hand, sometimes in some places over the past several decades, nearly pure MDMA has been available on the illicit market. Nonetheless, a buyer of Ecstasy may ingest, rather than MDMA, drugs such as ketamine, gamma-hydroxybutyrate (GHB), cathinone, ephedrine, caffeine, or any one of the so-called designer drugs, many of which are amphetamine derivatives. A consequence of this pharmacological chaos is that many of the hazards associated with the use of Ecstasy have been uncritically attributed to MDMA. This fact has been a boon for those who would continue the Schedule I status of MDMA and a bane for those who would explore its therapeutic potential. However, in contrast with recreational use where purity of the drug is uncertain, MDMA in clinical trials is FDA approved and of known composition.
The Early Response to Mendeleev’s Periodic System in Russia
Authors: Kaji Masanori , Brooks Nathan
Published: November 2020

Mendeleev’s first table of elements, entitled “An Attempt at a System of the Elements Based on Their Atomic Weight and Chemical Analogies,” was dated February 17, 1869. His first paper on the discovery, “The Correlation of the Properties and Atomic Weights of the Elements” (hereafter referred to as Paper I), was read in the meeting of the newly established Russian Chemical Society (RCS) on March 6 by Nikolai Aleksandrovich Menshutkin (1842–1907), the secretary of the Society for Dmitrii Ivanovich Mendeleev (1834–1907), who was not able to attend the meeting since he was visiting various cheese-making factories outside the city. The members of the Society who attended this meeting decided not to discuss Mendeleev’s paper, and it was tabled until the next meeting. The paper was published in the second/third combined issue of the first volume of the Society’s journal in May (Paper I). Paper I was the first public announcement of one of the most important dis­coveries in nineteenth-century chemistry: what would soon be called Mendeleev’s “periodic law.” However, the paper did not draw immediate attention from the chemists at the meeting. While this muted response was similar to the initial recep­tion of the periodic system in other countries, the reception of the periodic system in Russia was distinctive for various reasons. This paper will examine some of these factors first. The most obvious difference between the reception of the periodic system in Russia as compared to other countries is simply due to the fact that Mendeleev was Russian. Thus, the reception of the periodic system in Russia needs to be considered in the context of Mendeleev’s place in the Russian chemical community, as well as in intellectual terms. In 1869, at the time of Mendeleev’s first announcement about the periodic system, the Russian chemical community was in the process of formation.
Carbon–Carbon Bond Formation: The Bergman Synthesis of (+)-Fuligocandin B
Authors: Taber Douglass F.
Published: November 2020

Xile Hu of the Ecole Polytechnique Fédérale de Lausanne optimized (J. Am. Chem. Soc. 2011, 133, 7084) a Ni catalyst for the coupling of a Grignard reagent 2 with a secondary alkyl halide 1. Duk Keun An of Kangwon National University devised (Tetrahedron Lett. 2011, 52, 1718; Chem. Commun. 2011, 47, 3281) a strategy for the reductive coupling of an ester 4 with a Grignard reagent 2 to give the secondary alcohol. Daniel J. Weix of the University of Rochester added (Org. Lett. 2011, 13, 2766) the halide 7 in a conjugate sense to the bromoenone 6, setting the stage for further organometallic coupling. James Y. Becker of the Ben-Gurion University of the Negev effected (J. Org. Chem. 2011, 76, 4710) Kolbe coupling of the silyl acid 9 to give the decarboxylated dimer 10. Shi-Kai Tian of USTC Hefei showed (Chem. Commun. 2011, 47, 2158) that depending on the sulfonyl group used, the coupling of 11 with 12 could be directed cleanly toward either the Z or the E product. Yoichiro Kuninobu and Kazuhiko Takai of Okayama University added (Org. Lett. 2011, 13, 2959) the sulfonyl ketone 14 to the alkyne 13 to form the trisubstituted alkene 15. Jianbo Wang of Peking University assembled (Angew. Chem. Int. Ed. 2011, 50, 3510) the trisubstituted alkene 18 by adding the diazo ester 16 to the alkyne 17. Gangguo Zhu of Zhejiang Normal University constructed (J. Org. Chem. 2011, 76, 4071) the versatile tetrasubstituted alkene 21 by adding the chloroalkyne 19 to acrolein 20. Other more substituted acceptors worked as well. Chunxiang Kuang of Tongji University and Qing Yang of Fudan University effected (Tetrahedron Lett. 2011, 52, 992) elimination of 22 to 23 by stirring with Cs2CO3 at 115°C in DMSO overnight. Toshiaki Murai of Gifu University created (Chem. Lett. 2011, 40, 70) a propargyl anion by condensing 24 with 25 then adding 26. Xiaodong Shi of West Virginia University found (Org. Lett. 2011, 13, 2618) that the enantiomerically enriched propargyl ether 29 could be rearranged to the trisubsituted allene 30 with retention of the ee and with high de.
Reactions of Alkenes
Authors: Taber Douglass F.
Published: November 2020

Fung-E Hong of the National Chung Hsing University devised (Adv. Synth. Catal. 2011, 353, 1491) a protocol for the oxidative cleavage of an alkene 1 (or an alkyne) to the carboxylic acid 2. Patrick H. Dussault of the University of Nebraska found (Synthesis 2011, 3475) that Na triacetoxyborohydride reduced the methoxy hydroperoxide from the ozonolysis of 3 to the aldehyde 4. Reductive amination of 4 can be effected in the same pot with the same reagent. Philippe Renaud of the University of Bern used (J. Am. Chem. Soc. 2011, 133, 5913) air to promote the free radical reduction to 6 of the intermediate from the hydroboration of 5. Robert H. Grubbs of Caltech showed (Org. Lett. 2011, 13, 6429) that the phosphonium tetrafluoroborate 8 prepared by hydrophosphonation of 7 could be used directly in a subsequent Wittig reaction. Dominique Agustin of the Université de Toulouse epoxidized (Adv. Synth. Catal. 2011, 353, 2910) the alkene 9 to 10 without solvent other than the commercial aqueous t-butyl hydroperoxide. Justin M. Notestein of Northwestern University effected (J. Am. Chem. Soc. 2011, 133, 18684) cis dihydroxylation of 9 to 11 using 30% aqueous hydrogen peroxide. Chi-Ming Che of the University of Hong Kong devised (Chem. Commun. 2011, 47, 10963) a protocol for the anti-Markownikov oxidation of an alkene 12 to the aldehyde 13. Aziridines such as 14 are readily prepared from alkenes. Jeremy B. Morgan of the University of North Carolina Wilmington uncovered (Org. Lett. 2011, 13, 5444) a catalyst that rearranged 14 to the protected amino alcohol 15. A monosubstituted alkene 16 is particularly reactive both with free radicals and with coordinately unsaturated metal centers. A variety of transformations of monosubstituted alkenes have been reported. Nobuharu Iwasawa of the Tokyo Institute of Technology employed (J. Am. Chem. Soc. 2011, 133, 12980) a Pd pincer complex to catalyze the oxidative monoborylation of 16 to give 17. The 1,1-bis boryl derivatives could also be prepared. Professor Renaud effected (J. Am. Chem. Soc. 2011, 133, 13890) radical addition to 16 leading to the terminal azide 18.
C–O Ring Construction: The Reisman Synthesis of (–)-Acetylaranotin
Authors: Lambert Tristan H.
Published: November 2020

The Prins cyclization is a powerful approach for the construction of oxygen-containing heterocycles. B.V. Subba Reddy at the Indian Institute of Technology has reported (Tetrahedron Lett. 2012, 53, 3100) an approach to 2,6-dioxabicyclo[3.2.1]octanes 2 by way of a tandem Prins reaction/intramolecular acetalization of the diol 1 and a variety of aldehydes. Christine L. Willis of the University of Bristol utilized (Angew. Chem. Int. Ed. 2012, 51, 3901) nontraditional γ, δ-unsaturated alcohols 3 for a Prins-type strategy to access bicyclic heterocycles 5, while Zhenlei Song of Sichuan University employed (Angew. Chem. Int. Ed. 2012, 51, 5367) a bis(silyl) homoallylic alcohol 7 in the synthesis of structures such as 8, corresponding to the B ring of the bryostatins. In a mechanistically related process, the conversion of unsaturated ketones 9 to tetrahydropyranyl products 11 by treatment with a boronic acid 10 and triflic anhydride was described (Org. Lett. 2012, 14, 1187) by Aurelio G. Csáky at the Universidad Complutense in Spain. A powerful approach to heterocycles is via the ring expansion of smaller, and especially strained, ring systems. Jon T. Njardarson of the University of Arizona has been exploring such strategies and has reported (Angew. Chem. Int. Ed. 2012, 51, 5675) the conversion of vinyl oxetanes to dihydropyrans via catalysis by transition metals or Brønsted acids. The use of a chiral catalyst such as 13 allowed for the enantioselective conversion of divinyl oxetane 12 to enantioenriched dihydropyran 14. Meanwhile, Amir H. Hoveyda at Boston College and Richard R. Schrock at MIT have developed (J. Am. Chem. Soc. 2012, 134, 2788) a highly reactive and stereoselective catalyst for the ring-opening/cross-metathesis of several ring systems such as 15 with enol ethers. Notably, reactions occur rapidly (e.g., 10 min) using as little as 0.15 mol% catalyst. An alkynyl cyclopropyl ketone such as 17 can be converted (Angew. Chem. Int. Ed. 2012, 51, 4112) to products 18 by treatment with a gold/silver catalyst mixture, as shown by Zhongwen Wang at Nankai University. Notably, the oxabicyclic ring structure contained within 18 is present in a diversity of natural product structures.
Alkaloid Synthesis: Indolizidine 207A (Shenvi), (–)-Acetylaranotin (Reisman), Flinderole A (May), Isohaouamine B (Trauner), (–)-Strychnine (MacMillan)
Authors: Lambert Tristan H.
Published: November 2020

Ryan A. Shenvi at the Scripps Research Institute in La Jolla has reported (J. Am. Chem. Soc. 2012, 134, 2012) a procedure for the stereoselective formal hydroamination of aminodienes to produce indolizidines. The procedure involves an amine-directed hydroboration, followed by a B to N bond migration (cf. 2) that is induced with molecular iodine and sodium methoxide. The pyrrolidinyl alcohols 3 generated upon oxidation can then be converted by a Mitsunobu reaction to the target bicyclic structures, including indolizidine 207A. Jeremy A. May at the University of Houston has shown (J. Am. Chem. Soc. 2012, 134, 6936) that a biomimetic strategy to access members of the flindersial alkaloids is viable. Borrerine can be prepared in two steps from tryptamine and subsequently dimerized by treatment with acid. Notably, the exclusive formation of either flinderoles A and C or isoborreverine can be achieved by treatment with either acetic acid or BF3•OEt2, respectively. The different outcomes of these dimerizations are the result of competing formal [3+2] and [4+2] cycloaddition pathways. The unusual paracyclophane-containing alkaloid haouamine B has undergone (J. Am. Chem. Soc. 2012, 134, 9291) a structural revision by Eva Zubia at the University of Cádiz due to the total synthesis of the reported structure (now called isohaouamine B) by Dirk Trauner at the University of Munich. To construct the strained paracyclophane moiety, the iodoamine 4 was deprotected and cyclized to produce structure 5. Aromatization of the cyclohexenone ring then provided the energetic offset for the strain present in 6. This route provided useful quantities of isohaouamine B for biological testing. Few natural products have captured the imaginations of chemists more than strychnine, and some of the most impressive achievements in the field of total synthesis have come from those who have taken up this challenge. David W.C. MacMillan at Princeton University has designed (Nature 2011, 475, 183) an enantioselective approach that not only furnishes (–)-strychnine in 12 steps, but also provides rapid access to a range of other biosynthetically related yet structurally diverse alkaloids, including (–)-akuammicine, (+)-aspidospermidine, (+)-vincadifformine, and (–)-kopsanone.
Metal-Mediated Carbocyclic Construction: The Whitby Synthesis of (+)-Mucosin
Authors: Taber Douglass F.
Published: November 2020

Erick M. Carreira of ETH-Zürich generated (Org. Lett. 2012, 14, 2162) ethyl diazoacetate in situ in the presence of the alkene 1 and an iron catalyst to give the cyclopropane 3. Joseph M. Fox of the University of Delaware inserted (Chem. Sci. 2012, 3, 1589) the Rh carbene derived from 5 into the alkene 4 to give the cyclopropene 6, without β-hydride elimination. Masaatsu Adachi and Toshio Nishikawa of Nagoya University reduced (Chem. Lett. 2012, 41, 287) the enone 7 to give the cyclobutanol 8. Intramolecular ketene cycloaddition has been limited to very electron-rich acceptor alkenes. Xiao-Ping Cao and Yong-Qiang Tu of Lanzhou University devised (Chem. Sci. 2012, 3, 1975) a protocol that converted 9 into the cyclobutanone 10 with high diastereocontrol. The intermediate is the tosylhydrazone of the ketone, so a reductive workup would lead to the corresponding cycloalkane. Koichi Mikami of the Tokyo Institute of Technology added (J. Am. Chem. Soc. 2012, 134, 10329) alkyl cuprates to the prochiral enone 11 to give the enolate trapping product 13 in high ee and with high diastereocontrol. Marcus A. Tius of the University of Hawaii found (Angew. Chem. Int. Ed. 2012, 51, 5727) a Pd catalyst for the Nazarov cyclization of 14 to 15. Antoni Riera and Xavier Verdaguer of the Universitat de Barcelona prepared (Org. Lett. 2012, 14, 3534) 16 by enantioselective Pauson-Khand addition to tetramethyl norbornadiene. Conjugate addition followed by retro Diels-Alder could potentially lead to the cyclopentenone 17. The intermolecular Pauson-Khand cyclization often gives mixtures of regioisomers. José Barluenga of the Universidad de Oviedo demonstrated (Angew. Chem. Int. Ed. 2012, 51, 183) an alternative, the addition of an alkenyl lithium 19 to the Fischer carbene 18 leading to 20. Jian-Hua Xie and Qi-Lin Zhou of Nankai University hydrogenated (Adv. Synth. Catal. 2012, 354, 1105; see also Org. Lett. 2012, 14, 2714) the ketone 21 under epimerizing conditions to give the alcohol 22. Kozo Shishido of the University of Tokushima observed (Tetrahedron Lett. 2012, 53, 145) that the intramolecular Heck cyclization of 23 proceeded with high diastereocontrol. Zhi-Xiang Yu of Peking University devised (Org. Lett. 2012, 14, 692) an Rh catalyst for the cyclocarbonylation of 25 to 26.
Metal-Mediated Ring Construction: The Hoveyda Synthesis of (–)-Nakadomarin A
Authors: Taber Douglass F.
Published: November 2020

John F. Hartwig of the University of California, Berkeley effected (J. Am. Chem. Soc. 2013, 135, 3375) selective borylation of the cyclopropane 1 to give 2. It would be particularly useful if this borylation could be made enantioselective. Eric M. Ferreira of Colorado State University showed (Org. Lett. 2013, 15, 1772) that the enantomeric excess of 3 was transferred to the highly substituted cyclopropane 4. Antonio M. Echavarren of ICIQ Tarragona demonstrated (Org. Lett. 2013, 15, 1576) that Au-mediated cyclobutene construction could be used to form the medium ring of 6. Joseph M. Fox of the University of Delaware developed (J. Am. Chem. Soc. 2013, 135, 9283) what promises to be a general enantioselective route to cyclobutanes such as 8 by way of the intermediate bicyclobutane (not illustrated). Huw M.L. Davies of Emory University reported (Org. Lett. 2013, 15, 310) a preliminary investigation in this same direction. Masahisa Nakada of Waseda University prepared (Org. Lett. 2013, 15, 1004) the cyclopentane 10 by enantioselective cyclization of 9 followed by reductive opening. Young-Ger Suh of Seoul National University cyclized (Org. Lett. 2013, 15, 531) the lactone 11 to the cyclopentane 12. Xavier Ariza and Jaume Farràs of the Universitat de Barcelona optimized (J. Org. Chem. 2013, 78, 5482) the Ti-mediated reductive cyclization of 13 to 14. The hydrogenation catalyst reduced the intermediate Ti–C bond without affecting the alkene. Erick M. Carreira of ETH Zürich observed (Angew. Chem. Int. Ed. 2013, 52, 5382) that a sterically demanding Rh catalyst mediated the highly diastereoselective cyclization of 15 to 16. The ketone 16 was the key intermediate in a synthesis of the epoxyisoprostanes. Jianrong (Steve) Zhou of Nanyang Technological University used (Angew. Chem. Int. Ed. 2013, 52, 4906) a Pd catalyst to effect the coupling of 17 with the prochiral 18. Geum-Sook Hwang and Do Hyun Ryu of Sungkyunkwan University devised (J. Am. Chem. Soc. 2013, 135, 7126) a boron catalyst to effect the addition of the diazo ester 21 to 20. They showed that the sidechain stereocenter was effective in directing the subsequent hydrogenation of 22.
Diels-Alder Cycloaddition: (+)-Armillarivin (Banwell), Gelsemiol (Gademann), (+)-Frullanolide (Liao), Myceliothermophin A (Uchiro), Peribysin E (Reddy), Caribenol A (Li/Yang)
Authors: Taber Douglass F.
Published: November 2020

Martin G. Banwell of the Australian National University prepared (Org. Lett. 2013, 15, 1934) the enantiomerically pure diol 1 by fermentation of the aromatic precursor. Diels-Alder addition of cyclopentenone 2 proceeded well at elevated pressure to give 3, the precursor to (+)-armillarivin 4. Karl Gademann of the University of Basel found (Chem. Eur. J. 2013, 19, 2589) that the Diels-Alder addition of 6 to 5 proceeded best without solvent and with Cu catalysis to give 7. Reduction under free radical conditions led to gelsemiol 8. Chun-Chen Liao of the National TsingHua University carried out (Org. Lett. 2013, 15, 1584) the diastereoselective addition of 10 to 9. A later oxy-Cope rearrangement established the octalin skeleton of (+)-frullanolide 12. D. Srinivasa Reddy of CSIR-National Chemical Laboratory devised (Org. Lett. 2013, 15, 1894) a strategy for the construction of the angularly substituted cis-fused aldehyde 15 based on Diels-Alder cycloaddition of 14 to the diene 13. Further transformation led to racemic peribysin-E 16. An effective enantioselective catalyst for dienophiles such as 14 has not yet been developed. Hiromi Uchiro of the Tokyo University of Science prepared (Tetrahedron Lett. 2012, 53, 5167) the bicyclic core of myceliothermophin A 19 by BF3•Et2O-promoted cyclization of the tetraene 17. The single ternary center of 17 mediated the formation of the three new stereogenic centers of 18, including the angular substitution. En route to caribenol A 22, Chuang-Chuang Li and Zhen Yang of the Peking University Shenzen Graduate School assembled (J. Org. Chem. 2013, 78, 5492) the triene 20 from two enantiomerically pure precursors. Inclusion of the radical inhibitor BHT sufficed to suppress competing polymerization, allowing clean cyclization to 21. Methylene blue has also been used (J. Am. Chem. Soc. 1980, 102, 5088) for this purpose.
The Yamashita/Hirama Synthesis of Cortistatin A
Authors: Taber Douglass F.
Published: November 2020

A central challenge in the synthesis of the antiangiogenic cortistatin A 3 is the stereocontrolled assembly of the cycloheptene ring. Shuji Yamashita and Masahiro Hirama of Tohoku University solved (J. Org. Chem. 2011, 76, 2408) this problem by the addition of the intermediate radical from the reduction of 1 in an intramolecular sense to the cyclohexenone of 1 to give 2. The starting point for the synthesis was the enantiomerically enriched enone 4, prepared from the Hajos-Parrish ketone. Alkylation gave 6, which was reduced, after some experimentation, selectively to the trans-fused ketone 7. Pd-mediated oxidation of the silyl enol ether derived from 7 gave the enone, which was homologated to the aldehyde 8 by way of the corresponding enol triflate. Condensation with dihydroresorcinol 9 delivered the triene 10, which was carried on the iodide 1. Unexpectedly, 1 readily epimerized at the indicated stereocenter, presumably by way of an equilibrating Claisen rearrangement. Fortunately, when the solid iodide was maintained at-30oC for 12 h, the desired diastereomer became dominant. The free radical reduction then proceeded smoothly to give 2. To introduce the pendant isoquinoline of the natural product, 2 was protected and oxidized to 11. Reduction of the thiocarbamate derived from the tertiary alcohol 13, with H atom transfer to the more open face of the intermediate free radical, then delivered 14. To oxidize 14 to the enone 15, the ketone was deprotonated, then exposed to the Mukaiyama reagent 15. Nucleophilic epoxidation followed by reduction, following the Nicolaou precedent, then set the stage for selective opening with dimethylamine, to complete the synthesis of (+)-cortistatin A 3.
The Qin Synthesis of (+)-Gelsemine
Authors: Taber Douglass F.
Published: November 2020

(+)-Gelsemine 3 has no particular biological activity, but its intricate architecture continues to inspire the ingenuity of organic synthesis chemists. Yong Qin of Sichuan University devised (Angew. Chem. Int. Ed. 2012, 51, 4909) an enantiospecific synthesis of 3, a key step of which was the cyclization of 1 to 2. The starting material for the synthesis was the inexpensive diethyl tartrate 4, which was converted over six steps into the N-sulfonyl aziridine 5. The addition of 6 was highly regioselective, leading, after N-methylation, to the alkyne 7. After alcohol protection, the sulfonyl group was smoothly removed by sonication with Mg powder in methanol. Addition to acryonitrile then gave 8. Semihydrogenation of 8 set the stage for construction of the lactone 1. The anion of 1, generated by exposure to LDA, cyclized to 2 with significant diastereoselectivity. The lactone of 2 was selectively reduced with Dibal, to give an aldehyde that was protected as the acetal. The exposed primary alcohol was then oxidized to the aldehyde 9. Condensation of 9 with the enolate of 10 followed by dehydration delivered the alkene 11, with the stage set for a second intramolecular nitrile anion addition. In the event, the cyclization of 11 delivered 12, the wrong diastereomer. This was corrected by selenation and oxidation to give an alkene, which was hydrogenated to 13. Exposure to acid deprotected both the MOM group of 13 and the acetal, then promoted cyclization to 14. Reduction of the nitrile to the aldehyde followed by methylenation completed the synthesis of (+)-gelsemine 3. It should be noted that the hydrogenation to form 13 had to be carried out carefully to avoid premature removal of the N-methoxy group. That group was critical for the successful conversion of 13 to 14.
What Is Pyrite?
Authors: Rickard David
Published: November 2020

In this chapter I show how pyrite was at the heart of our early understanding of the composition of substances and how it was central to the acceptance of the revolutionary idea that substances have fixed compositions. This, in turn, was the evidential basis for the modern atomic theory. Taxonomists will argue that naming things accurately is important since otherwise no-one will know what you are talking about. They would disagree with Shakespeare that a rose would smell as sweet whatever it was called on the grounds that you would not know that a rose was being described. Even so, the only reason things are named is because of need. Thus Homer did not have a word for blue because he never needed it: the blue sea became wine-dark, for example. By contrast, contemporary ancient Egyptians had a word for blue because they used the blue mineral lapis lazuli for decoration. The mineral pyrite has been employed by humankind for millennia, and it needed a name. Its long history means that a variety of terms have been used to describe it, often reflecting the technology available at the time. In order to understand the role that pyrite has played in the past, we need to interpret the various names given to this mineral by earlier authorities. This problem is compounded since its history is determined by ancient texts and these were commonly written down by scribes from direct dictation. The scribes rendered the sounds of words as best they could within the limitations of the current orthography. Before the advent of printing, copyists made reproductions of these original texts according to the customs and mores of their local culture. The texts that have come down to us are usually the result of the work of several generations of copyists, and the interpretations become like a game of Chinese whispers. Whether or not a word in an ancient text means pyrite is, at best, a matter of relating it to a description that reflects key properties of the mineral. At worst it may mean probing the etymology of the word and considering its context.
The Environmental Protection Agency: 1970–2010
Authors: Conant James K. , Balint Peter J.
Published: November 2020

The official birthdate of the U.S. Environmental Protection Agency (EPA) is December 2, 1970. On that day the Senate confirmed William Ruckelshaus, President Nixon’s nominee to be the administrator of the new agency, and the “EPA opened for business in a tiny suite of offices at 20th and L Streets in Northwest Washington, DC.” The new agency took over programs and offices related to environmental protection previously operating in the Department of the Interior, the Department of Agriculture, the Department of Health, Education, and Welfare, the Food and Drug Administration, the Atomic Energy Commission, and the Federal Radiation Council. In this chapter, we examine and attempt to explain what happened to this major regulatory agency over the forty-year period from its birth in 1970 to 2010. In doing so, we test hypotheses that follow from the four categories of theoretical agency life cycle models introduced in Chapter 3. These models differ in their predictions for the trajectories of federal agencies. The biological model predicts that agencies will grow rapidly during their early life before reaching a relatively stable maturity. Over subsequent decades agencies may carry on indefinitely with declining vigor, or be absorbed into other agencies, or die, although scholars debate both the process and probability of agency mortality. The partisan political model predicts a more turbulent life history for agencies in which changing party control of Congress and the White House will buffet government organizations more or less routinely. According to this model, federal agencies will often be caught in the middle of partisan ideological battles over the importance and value of the social functions they were created to address. The incremental model suggests that the best predictor of how agencies will fare in the near future is how they have fared in the recent past. That is, agencies tend to be insulated from external political and economic fluctuations and therefore generally experience relatively minor changes over time to their budgets and operations. The issue-attention model predicts that agencies’ fortunes are tied to the vagaries of current events.
On to Wisconsin, the Dairy State
Authors: Wurster Charles F.
Published: November 2020

EDF was only a few months old with the DDT agitation still under way in Michigan when a phone call arrived from Lorrie Otto, an environmental leader in Milwaukee, Wisconsin (Fig. 4.1). Lorrie explained that DDT was to be used for attempted Dutch elm disease control in Milwaukee, and she wanted EDF to come to Wisconsin and stop it. She had been reading about our fireworks on Long Island and in Michigan and figured some of that might be good for Wisconsin. Other considerations were also favorable about Wisconsin. The use of DDT leads to contamination of meat, eggs, milk, and other dairy products, and the dairy industry is large and important in Wisconsin. Agriculture was therefore split in that state: One component wanted to use DDT on crops and trees, while the dairy industry wished to avoid DDT contamination of its products. Agriculture would not present a unified force on behalf of DDT, as it would in most states. The environmental movement was unusually strong in Wisconsin, and Lorrie Otto pledged to EDF the statewide support of the Citizens Natural Resources Association (CNRA). CNRA would raise money and provide all additional logistic support that might be necessary during whatever proceedings might develop. If EDF was going to make a difference on the national scene, this seemed like an invitation not to be refused. So here was an opportunity to stir up trouble again with an increase in complexity and confusion. On October 2, 1968, EDF filed a lawsuit in Federal Court in Milwaukee that was quite similar to the one filed nearly a year earlier in Michigan. It sought to block the Michigan Department of Agriculture (MDA) from applying dieldrin in Michigan against Japanese beetles (same case, same application as postponed last year) and to stop Milwaukee from spraying DDT on its elm trees. The allegations were the same: both DDT and dieldrin would kill nontarget birds and mammals, and both would threaten reproduction of the Coho salmon in Lake Michigan hatcheries.
Ruckelshaus Decides
Authors: Wurster Charles F.
Published: November 2020

All parties to the hearings knew that on June 14, 1972, at exactly 10 a.m., the door of the EPA administrator’s office would open and out would come someone to distribute copies of the decision on the future of DDT. Nobody knew what was in it, but all parties figured there would be something they would not like and would therefore want to appeal it to an appeals court. Appeals could be heard by any of several federal appellate courts around the country. More important, the first appeal made to any court would likely determine the location or venue where the appeal would be heard. The DDT proponents knew they had done poorly in the DC Court of Appeals, so they wanted to get their appeal out of DC; surely the cotton belt would be best. So they were waiting for that door to open with an open telephone line to the 5th Circuit Federal Court of Appeals in New Orleans, Louisiana. We knew what they were up to, so we were determined to file our appeal very quickly with the US Court of Appeals for DC, where we had done very well. That was not a simple procedure. Cell phones did not exist in those days. The EPA administrator’s door opened, the papers came out, and both appeals were rushed to the respective courts of appeal. Not a second was wasted to see what was in the decision. EDF attorney Bill Butler flashed the appeal on a pay phone, which had an open line to another pay phone in the DC Court of Appeals building near the clerk’s office, where EDF secretary Marie Bauman filed the EDF appeal. Each side claimed it had gotten to its preferred appeals court first. The DDT proponents said the case would move to New Orleans for the appeal. Much controversy and confusion ensued. Finally, it was decided that the clocks were not properly synchronized and that EDF had won the rapid communication derby: The case would stay in Washington, DC.
Hope for Redemption
Authors: Revesz Richard , Lienke Jack
Published: November 2020

The Walter C. Beckjord Generating Station sits on the banks of the Ohio River, less than twenty miles southeast of Cincinnati, in Clermont County, Ohio. Beckjord offers a near-perfect case study of the costs of grandfathering. Construction of the plant was announced in November 1948, and its first 100-megawatt coal unit was operational by June 1952. Five additional units came online between 1953 and 1969. Because the units were constructed prior to 1971, all were exempt from the EPA’s New Source Performance Standards. For most of the 1970s, they also managed to avoid complying with any emission limitation under Ohio’s implementation plan for meeting the sulfur dioxide NAAQS, even though Ohio’s original plan, approved by the EPA in 1972, would have subjected Beckjord to a state emission standard—1.6 pounds of SO2 per million Btus of heat input—that was only 33 percent less stringent than the federal new-source standard of 1.2 lbs/MMBtu. In 1973, Ohio utilities convinced the U.S. Court of Appeals for the Sixth Circuit to invalidate the Ohio plan on procedural grounds. The court ordered the EPA to hold an additional hearing at which regulated plants could voice their objections, but before the agency could oblige, the governor of Ohio withdrew the plan from consideration. A year later, Ohio submitted a far less stringent proposal that would have allowed Beckjord to continue emitting at its uncontrolled level: 4.8 lbs/MMBtu. But that plan, too, was struck down on procedural grounds, this time by a state environmental review board. In 1976, after Ohio failed to offer any replacement for its second proposal, the EPA stepped in with a federal plan that would limit Beckjord’s emissions to 2.02 lbs/MMBtu. (This, according to the latest EPA computer modeling, was the level necessary for Ohio to attain the sulfur dioxide NAAQS.) After yet more litigation by Ohio utilities—including Beckjord’s owner, Cincinnati Gas & Electric—the bulk of the federal plan was upheld in 1978. (In rejecting the utilities’ challenge, the Sixth Circuit noted that Ohio was the only state in the country that still lacked an enforceable SO2 implementation plan.)
Advances in Neuropsychological Assessment of Attention
Authors: Díaz-Orueta Unai
Published: November 2020

Attention is one of the most basic cognitive processes and is a prerequisite for the use of more complex functions, since it is not possible to evaluate perception or memory processes without keeping in mind attention issues (Amador, Forns, & Kirchner, 2006). The ability to maintain an appropriate level of attention is basic for education and learning, especially during childhood and school age. With the aim of studying attention separately from other cognitive functions, the so-called continuous performance tests (CPT) were created. The first series of CPTs were developed by Rosvold, Mirsky, Sarason, Bransome, and Beck (1956) to study vigilance in adults with acquired brain injury (Riccio, Reynolds, & Lowe, 2001), more specifically, persons with seizures (Amador, Forns, & Kirchner, 2006). Nowadays, CPTs are still one of the most widely used measures for the assessment of attention and processing speed. Briefly, it can be said that a CPT is a group of paradigms to evaluate attention, inhibitory response or disinhibition (a component of executive control that provides information about the subject’s impulsivity), and processing speed. Basically, CPTs rely on the rapid, random presentation of a series of stimuli to which the subject must respond following instructions given at the beginning of the test. The main value of CPTs is their empirical support. Diverse CPT paradigms have consistently demonstrated their sensitivity for a great variety of both neurological and psychiatric disorders, in adults and in children. Frequently, CPTs also use a continuous vigilance task, in order to obtain quantitative information about the individual’s ability to sustain attention in time. From its creation, the CPT paradigm has been used with many variants of its task component. Greenberg and Walkman (1993) found up to 100 different versions of CPT in use. Historically, when Rosvold and his collaborators introduced the test, they had the goal of measuring correct answers provided by the subject as an indicator of selective attention. With subsequent experimentation, other measures, such as processing speed, impulsivity, inattention, and sustained attention, divided or alternate, have been included.
The United States of Vanished Wetlands
Authors: Levy Sharon
Published: November 2020

Before he became a revolutionary general and the nation’s first president, George Washington was a destroyer of wetlands. In 1763, he surveyed the edges of a million-acre expanse of wet forest that lay along the Virginia–North Carolina state line. He described the Great Dismal Swamp as a “glorious paradise” full of wildfowl and game. Still, he seemed to have no qualms about dismantling Eden. In 1764 he applied with five partners for a charter to create a business called “Adventurers for draining the great Dismal Swamp.” Their goal was to chop down and sell the timber from majestic cypress and cedar trees, then to plow the land for crops. The brutal work of digging drainage ditches and canals was done by slaves. By the time of the Revolutionary War, the Adventurers Company was producing 8 million shingles a year for sale—valuable slivers of wood cut from the swamp’s enormous bald cypress trees. There was profit in undoing wetlands. Draining a wetland also seemed to make a place healthier. People who colonized swampy land were plagued by a dreadful illness, one that often killed, and left survivors with recurring bouts of a bonerattling fever. Malaria—the name itself means “bad air”—was believed to be triggered by poisonous vapors rising from still waters. The drainage and destruction of wetlands was an unwritten founding principle of the US. The pattern began with some of the earliest European settlers. Well before the colonies won their independence, the loss of wetlands had led to pollution that changed the ecology of rivers and bays. Over the centuries, wetlands loss and water pollution have accelerated in tandem, driven by the need for farmland, the urge for profit, and the fear of disease. The history of these interwoven changes on land and underwater begins in the Chesapeake Bay, the site of the first permanent British colony in America. In the summer of 1608, Captain John Smith and the colonists of Jamestown were starving.
Geopolitical Catastrophe
Authors: Toal Gerard
Published: November 2020

On April 25, 2005, President Vladimir Putin addressed the Federal Assembly of the Russian Federation. In his lengthy speech Putin laid out a series of priorities for the Russian state in the coming decade. These priorities were not new—he had spoken about them in a similar address the year before—and their central aim was well known, “to build,” as he put it in his address, “an effective state system within the current national borders.” However, it was not Putin’s discussion of democracy and corruption in state institutions that generated headlines in the Western media. Instead it was Putin’s prologue for his reform agenda: . . . Above all, we should acknowledge that the collapse of the Soviet Union was a major geopolitical disaster of the century. As for the Russian nation, it became a genuine drama. Tens of millions of our co-citizens and compatriots found themselves outside Russian territory. Moreover, the epidemic of disintegration infected Russia itself. Individual savings were depreciated, and old ideals destroyed. Many institutions were disbanded or reformed carelessly. Terrorist intervention and the Khasavyurt capitulation [the agreement that ended the first Chechen war] that followed damaged the country’s integrity. Oligarchic groups—possessing absolute control over information channels— served exclusively their own corporate interests. Mass poverty began to be seen as the norm. And all this was happening against the backdrop of a dramatic economic downturn, unstable finances, and the paralysis of the social sphere. Many thought or seemed to think at the time that our young democracy was not a continuation of Russian statehood, but its ultimate collapse, the prolonged agony of the Soviet system. But they were mistaken. . . . Putin’s rhetorical device was a conventional decline-and-renewal trope, describing the era of national decline and humiliation that set the stage for his heroic mission of restoring Russia’s strength and capacity. However, Associated Press and BBC news service reports on the speech focused only on one phrase, to which they gave a different translation from that released by the Kremlin (cited above).
Geopolitics Thick and Thin
Authors: Toal Gerard
Published: November 2020

On November 24, 2015, a Turkish F-16 fighter jet shot down a Russian Sukhoi Su-24M aircraft on the Syria-Turkey border. For seventeen seconds the Russian aircraft crossed the southern tip of a salient of Turkish territory that Syria claimed rightfully belonged to it. Two Russians ejected from the plane over Syria. A local Turkmen militia, commanded by a Turkish citizen, fired at the aviators, killing one. A second Russian serviceman was killed during a rescue mission to save the surviving aviator. The incident, recorded on radar systems by many countries and partially captured on video camera, was the first time since the Korean War that a North Atlantic Treaty Organization (NATO) country’s fighter jet destroyed a Soviet/Russian Air Force aircraft. Fortunately the event did not escalate into a full-blown NATO Russia crisis, although with tensions high over the Ukraine crisis and two authoritarian leaders at loggerheads, it could well have done so. There were background accusations. Turkish president Erdoğan was aggrieved that Russia was bombing co-ethnic kin in its southern near abroad while aiding Kurdish separatists, while Russian president Putin saw Turkey as an accomplice of international terrorists. Entwined territorial and terrorist anxieties, as well as near abroad insecurities, preoccupied both men. Had Russia responded with force against Turkey, this could have triggered Article V of NATO’s Washington Treaty, and NATO members would have faced the prospect of war with Russia over a tiny piece of territory in the Middle East most knew nothing about. Relations between the NATO alliance and Russia are now at their lowest point since the collapse of the Soviet Union. Airspace violations, incidents at sea, military training exercises, and hybrid war hysteria have kept tensions high. After Crimea, NATO moved to strengthen its capacity to respond to perceived Russian encroachment on the Baltic countries. The Obama administration’s European Reassurance Initiative was launched in June 2014 with a $1 billion budget for training and temporary rotations. In a speech in Riga in September 2014, President Obama declared: “We’ll be here for Estonia.